Access the full text.
Sign up today, get DeepDyve free for 14 days.
Background Alzheimer’s disease (AD) is the core cause of dementia in elderly populations. One of the main hall- marks of AD is extracellular amyloid beta (Aβ) accumulation (APP-pathology) associated with glial-mediated neu- roinflammation. Whole-Body Vibration ( WBV ) is a passive form of exercise, but its effects on AD pathology are still unknown. Methods Five months old male J20 mice (n = 26) and their wild type ( WT ) littermates (n = 24) were used to inves- tigate the effect of WBV on amyloid pathology and the healthy brain. Both J20 and WT mice underwent WBV on a vibration platform or pseudo vibration treatment. The vibration intervention consisted of 2 WBV sessions of 10 min per day, five days per week for five consecutive weeks. After five weeks of WBV, the balance beam test was used to assess motor performance. Brain tissue was collected to quantify Aβ deposition and immunomarkers of astrocytes and microglia. Results J20 mice have a limited number of plaques at this relatively young age. Amyloid plaque load was not affected by WBV. Microglia activation based on IBA1-immunostaining was significantly increased in the J20 animals compared to the WT littermates, whereas CD68 expression was not significantly altered. WBV treatment was effective to ameliorate microglia activation based on morphology in both J20 and WT animals in the Dentate Gyrus, but not so in the other subregions. Furthermore, GFAP expression based on coverage was reduced in J20 pseudo-treated mice compared to the WT littermates and it was significantly reserved in the J20 WBV vs. pseudo-treated animals. Further, only for the WT animals a tendency of improved motor performance was observed in the WBV group compared to the pseudo vibration group. Conclusion In accordance with the literature, we detected an early plaque load, reduced GFAP expression and increased microglia activity in J20 mice at the age of ~ 6 months. Our findings indicate that WBV has beneficial effects on the early progression of brain pathology. WBV restored, above all, the morphology of GFAP positive astrocytes to the WT level that could be considered the non-pathological and hence “healthy” level. Next experiments need to be performed to determine whether WBV is also affective in J20 mice of older age or other AD mouse models. *Correspondence: Tamas Oroszi firstname.lastname@example.org; email@example.com Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 2 of 12 Keywords Passive exercise, Neuroinflammation, Amyloid beta, J20 mice, Motor coordination Introduction of synaptic and/or neural plasticity and spatial mem- Alzheimer’s disease (AD) has been identified as the most ory, and in alleviated pathological changes of glial cells prevalent type of dementia . The major pathological [20–25]. hallmarks of AD are extracellular amorphous amyloid To the best of our knowledge, and confirmed by a plaques aggregated of misfolded amyloid beta peptides recent review , the therapeutic effects of WBV have and intracellular neurofibrillary tangles consisting of never been investigated in the context of AD pathophysi- hyperphosphorylated TAU proteins [1, 2]. However, ology. However, similar alternative therapies based on there is growing evidence that the involvement of glial- transcranial ultrasound and auditory stimulation proved mediated neuroinflammation may also play an important the therapeutic efficacy of mechanical waves to mitigate role in the pathogenesis of AD [3–8]. AD pathophysiology. Given the potential significance of Given the high complexity and serious consequences WBV for neural protection, we hypothesized that WBV of AD, there has been a broad range of scientific inquir - may beneficially modulate the glial activation (known to ies for pharmacological, as well as non-pharmacologi- be critically involved in AD pathology; see Rodríguez- cal treatment strategies [9, 10]. Ample meta-analytical Giraldo et al., 2022 for review ) and amyloid beta reviews have summarized the effects of regular physical plaque formation in the hippocampus of transgenic activity (PA) on the symptoms and progression of AD human APP-J20 mice, a well-known model of AD . [11–13]. Although it is important to note that these stud- To achieve this aim, we evaluated a five-week long WBV ies often demonstrated inconsistent results and do not protocol in five months-old transgenic human APP-J20 show unanimity, a growing body of evidence support the mice with the main focus on AD molecular pathophysiol- potential efficiency and value of regular and moderated ogy. Further, since WBV has been widely acknowledged PA to prevent and/or slow the progression of AD. Further, to improve muscle parameters, minor attention was also regular PA promotes neurogenesis, synaptic plasticity paid to the evaluation of motor performance. The age of and angiogenesis via increases in the level of neurotrans- five months was chosen to start the experiment because mitters and neurotrophic factors [12, 13]. The findings at this age J20 mice show an early, but detectable age- of these studies indicate that amyloid plaque formation related deficit in cognitive and behavioral performance and AD-related neuroinflammation could be reduced [28–31], as well as in the progression of neuroinflamma - by these factors. Active exercise may therefore be a via- tion and plaque formation . ble intervention to trigger anti-inflammatory effects to ameliorate amyloid plaque formation. Pharmacological Materials and methods and non-pharmacological AD treatments recently focus Animals more on the function of astrocytes, although their role Twenty-six transgenic hAPP-J20 male mice (PDGFB- entails a complex balance between neurotoxic and neu- APPSwInd; C57Bl6/J background) and 24 male wild type roprotective effects depending on the disease stage and (WT) littermates (C57Bl6/J) serving as healthy controls microenvironmental factors (Rodríguez-Giraldo et al. were used in this experiment. The age of these animals and references therein ). Moreover, there is a growing was 5 months at the start of the experiment. Both J20 need for alternative exercise strategies to support popu- and WT mice were randomly allocated to a WBV group lations who are unable and/or unmotivated to perform [WBV—J20 (n = 13) and WBV – WT (n = 12)] or a con- sufficient PA due to their limited cognitive and/or motor trol group [pseudo WBV—J20 (n = 13) and pseudo WT capabilities. (n = 12)]. Pseudo control mice were subjected to the Whole body vibration (WBV), a form of passive exer- same environmental stimuli, including placement on cise using mechanical vibration platforms, may provide the vibration plate and sound of the vibration plate, but an alternative for PA. Benefits of WBV in older popula - were not exposed to vibration. Animals were individu- tions are reflected by improved general fitness, mobility ally housed during the intervention period. Individual and balance [15, 16]. In rodents, WBV is able to increase housing started one week before the start of the inter- neuromuscular dynamics and muscle strength , to vention. Food and water were available ad libitum. Ani- improve adipose tissue dysfunction and glucose metab- mals were housed under standard laboratory conditions olism , and to promote muscle healing . Recent (12/12 dark—light cycle (lights on at 9:00 a.m.), tempera- animal studies have shown that vibration stimulates hip- ture (22 ± 1 °C) and humidity control (50 ± 10%)). Health pocampal functioning reflected in improved modulation status of the animals was checked daily and their body Or oszi et al. Behavioral and Brain Functions (2023) 19:5 Page 3 of 12 weight was registered each week by the researchers. All WBV session, mice were randomly placed into these experimental procedures were evaluated and approved individual compartments and were exposed to constant by the national Central Authority for Scientific Proce - vertical vibrations with a frequency of 30 Hz, an ampli- dures on Animals (CCD) and by the local Institutional tude of 50 micron (100 micron peak-to-peak displace- Animal Welfare Body of University of Groningen (IvD). ment) and of a sinusoidal nature. These parameters of vibration were verified by additional measurements using Whole‑body vibration procedure a 3D-accelerometer . The individual compartments We adhered to the new reporting guidelines for WBV and the cage were cleaned with 70% ethanol and dry studies in animals . Animals were exposed to a vibra- paper tissue between each training session. tion session of 10 min twice per day (i.e.: at 10 a.m. and Animals did not receive prior habituation to the experi- 16 p.m.), five times per week during 5 consecutive weeks mental settings. Both J20 and WT mice showed slightly (Fig. 1A). Furthermore, animals also received two WBV exited behavior during the first week of intervention. This days on week 6, but only one session on the second general unprompted activity was reduced from the sec- day (i.e.: WBV session at 10 a.m.; 24 h before sacrifice). ond week onwards. Some escape attempts (i.e.: jumping) The WBV device has been described before [34, 35]. In were recognized in the J20 mice during the entire inter- short, this device consists of an oscillator (LEVELL R.C. vention. Similarly, a significantly higher degree of def - Oscillator Type TG200DMP), a power amplifier (V406 ecation (i.e.: number of pellets) was observed in both J20 Shaker Power Amplifier) and a cage (44.5 × 28 × 16 cm) and WT mice after the WBV sessions in the first week of separated by 12 removable compartments (6.5 × 7.5 × 20) intervention, which seemed to be normalized only in the attached to the oscillator. Throughout a WBV/pseudo WT mice from the second week onwards. In contrast, J20 Fig. 1 Experimental design (A): 5 months old male hAPP-J20 mice and their wild ( WT ) littermates underwent 5 weeks of whole body vibration intervention ( WBV ) with twice daily session of 10 min exposure, five times per week (gray color marks the days of treatment). After 5 weeks, balance beam test was performed to assess motor coordination. Animals were terminated on week 6 at the age of ~ 6.5 months and brain tissue was collected for immunohistological analyses. Eec ff ts of intervention (pseudo vs. WBV ) and genotype (J20 vs. WT ) on body weight (B), motor performance (C) and plaque load (D). WT animals showed significatly higher body weight during the intervention compared to the J20 animals (B). Walking distance in the balance beam test was only significantly improved in the J20 animals compared to the WT (C). Amyloid plaque deposition in the hippocampus was not significantly affected by WBV intervention (D). Images of 6e10 were taken about the whole hippocampus at 50 × magnifications to visualze total amyloid plaque distribution (E), representative images of areas marked by + are depicted in D. Data are depicted as mean ± SEM. ** indicates: P < .01. Scale bars in D are 50 um and in E are 500 um Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 4 of 12 mice showed this higher degree of defecation after each 1:2500) in 0.01 M phosphate buffer saline (PBS) contain - training session throughout the entire intervention. All ing 1% bovine serum albumin (BSA) and 0.1% Triton-X vibration sessions were performed in the housing room (TX) or 2) Rat anti CD68 (BioRad, MCA1957GA; 1:1000) of the animals. Finally, the animals did not show any kind in 0.01 M tris buffered saline (TBS) with 5% BSA, 5% nor - of acute, short-term and/or long-term side effects by mal donkey serum (NDS). vibration. Astrocyte detection. Glial fibrillary acidic protein (GFAP) immunohistochemistry was performed to detect Balance beam astrocyte volume. Sections were pre—incubated in TBS The balance beam test was conducted after 5 weeks of containing 3% BSA and 0.1% TX followed by incubation WBV treatment to assess sensorimotor coordination of primary antibody (Cell Signaling, E4L7M, 1:10000). with main focus on the functionality of hind limbs . Plaque detection. Beta amyloid 1–16 (6E10) was stained A 1 m long wooden beam (with diameter of 4.5 mm) to detect plaque deposition in the hippocampus. Sections was placed horizontally 60 cm above the floor. The home were pre-incubated in 0.01 M TBS with 0.1% TX and 3% cage of the tested animal was positioned at the end of normal goat serum before the overnight incubation of the beam, serving as motivation and target factor for the primary antibody (BioLegend, SIG-39320; 1:2000). animal. In addition, prior to all stainings, endogenous peroxi- Mice were familiarized to the experimental setup by dase activity was blocked by hydrogen peroxidase (H O ) 2 2 two progressive trials (placed on the beam 10 cm and (0.3% for IBA1, GFAP and 6e10; 1% for CD68). For detec- 40 cm away from the target) and subsequently per- tion, we used biotinylated anti-mouse secondary anti- formed four test trials (at 100 cm distance), with 30 s bodies (IBA1 and GFAP: Goat Anti Rabbit 1: 500; CD68: break between all trials to ensure enough recovery to Mouse Anti Rat 1:500; 6E10: Goat Anti Mouse 1:400) avoid potential injuries induced by muscle fatigue. Video followed by processing with ABC kit (Vectastain ABC records were taken during the procedures, which were kit, Vector Laboratories) and developed our signal with independently analyzed by two researchers. Time needed diaminobenzidine (Sigma Fast, Cat: D4418) and 0.1% to cross the beam served as measure of performance and H2O2. All sections were intensively washed during the the mean of the three best trials was used as final out - staining processes in PBS or TBS. Sections were mounted come variable. If an animal was unable or unwilling to on gelation-coated slides, and placed overnight in a dry- cross over the beam it was excluded from the final statis - ing cabinet. Finally, sections were dehydrated in graded tical analysis (1 animal from the pseudo WBV/J20 group; solutions of ethanol and xylol and cover slipped. 1 animal from the WBV/WT group; 3 animals from the pseudo WBV/WT group). The beam was cleaned by 70% Microscopy ethanol and dry paper tissue after each animal. Number of microglia, cell body size, dendrites size and total coverage were determined in the Cornu Ammonis Immunohistochemistry 1 (CA1), Cornu Ammonis 3 (CA3), Dentate Gyrus (DG) Mice were anesthetized with pentobarbital and tran- and Hilus regions of the hippocampus based on the IBA1 sracially perfused with saline and 4% paraformaldehyde staining (200 × magnification). Since microglia activa - (PFA) twenty-four hours after the last WBV session. tion based on morphology is defined as shortened den - Brain tissue was harvested and postfixed by 4% PFA for dritic processes and increased cell body size, the ratio of 24 h before being transferred to phosphate buffer (PB) for the cell body to total cell size was calculated (see  for 3 days. After 3 days of washing, brains were dehydrated details) as the outcome measure of microglia activation. by 30% sucrose solution and frozen by liquid nitrogen. The coverage (% of the area of interest covered by the Brains were stored at − 80 °C until coronal sectioning immunostaining) of CD68 and GFAP positive cells were (20 μm) on a cryostat. Immunohistochemistry was per- determined in the CA1, CA3, DG and Hilus regions formed to determine microglia and astrocyte features, as (20 × magnification). Similarly, coverage of 6E10 was well as plaque deposition in the dorsal hippocampus. Free measured in the dorsal hippocampus (40 × magnifica - floating sections were used for all staining procedures. tion). All analyses were performed by Image J software. Microglia detection. Ionized calcium binding adaptor molecule 1 (IBA1) staining was performed to visualize Statistical analysis the morphological state of microglia cells; and cluster of Statistical analysis was performed by Statistica 13.2 differentiation factor 68 (CD68) was done to determine software. 2 × 2 factorial ANOVAs were performed with the level of microglia activation biochemically. Sections intervention (vibration/pseudo vibration) and genotype were incubated for 3 days at 4 °C by the following pri- (J20/WT) as factors and, in case of significant interven - mary antibodies: 1) Rabbit anti IBA1 (Wako, SKN4887, tion x genotype interaction, followed by Tukey’s post Or oszi et al. Behavioral and Brain Functions (2023) 19:5 Page 5 of 12 hoc test to reveal statistical differences between the four pseudo-WBV treated J20 groups (Fig. 1D). Representa- groups in balance beam performance, IBA1, GFAP and tive images of amyloid plaque load are depicted in Fig. 1E. CD68 stainings. In addition, amyloid plaque deposition between the two J20 groups was compared using inde- pendent T-tests. Mixed design repeated measurements Microglia ANOVA was performed with intervention (WBV, pseudo To determine whether differences in microglia activation WBV) and genotype (J20, WT) as between-subjects fac- in the subregions of hippocampus (CA1, CA2, DG and tors and time course (week 1–5) as within-subjects factor Hilus) existed across genotype and WBV intervention, to analyze differences in body weight. Statistical signifi - activated microglia were identified by the expression of cance was set at p < 0.05. Graphs were created by Graph- IBA1 and CD68 positive cells; two frequently used mark- Pad Prism 8 software. Descriptive data were expressed as ers for microglia. mean ± SEM. Morphological parameters of microglia based on the IBA1 immunostaining were determined including num- ber, total coverage, cell body and dendrites area in the Results CA1, CA3, DG and Hilus hippocampal subregions. Rep- Body weight and motor performance resentative images of IBA1 expression in the Hilus sub- Mixed design repeated measures ANOVA showed a region are visualized in Fig. 2A. Significantly decreased significantly higher body weight in the WT groups total coverage and increased cell body size were detected compared to the J20 animals (main effect genotype: in the J20 animals compared to the WT controls in all F = 15.060; p < 0.001) (Fig. 1B). In addition, a strong (1.46) hippocampal subregions. It was also observed that WBV tendency of lower body weight was observed in the WBV significantly ameliorated the size of dendritic processes treated groups compared to the pseudo-WBV groups in the CA1 (Main effect intervention: F = 5.636; (main effect intervention: F = 3.978; p = 0.052). A (1.40) (1.46) p = 0.022) and DG subregions (Main effect interven - significant effect of time course was also revealed (main tion: F = 15.15; p < 0.001) (Fig. 2C). Microglia num- effect time course: F = 4.871; p < 0.001). Further, the (1.40) (5.230) ber was not significantly altered. These morphological interaction of genotype*time course showed significant outcomes are summarized in Table 1. Furthermore, difference (intervention genotype x time interaction: microglia activation was calculated based on the IBA1 F = 2.788; p = 0.018) and additional post-hoc analy- (5.230) expression as the ratio of the cell body to total cell size. sis revealed decreased body weight in the WT animals Microglia activation of the 4 investigated subregions are for week 1 vs. week 3–6 (post hoc p < 0.05), but not in the summarized in Fig. 2B. Significantly higher degree of J20s. microglia activation was detected in the J20 groups com- The balance beam test was used in week 5 to assess pared to their WT littermates in the CA1, CA3, DG and motor coordination and functionality of primarily the Hilus subregions (Fig. 2B). In addition, decreased micro- hind limbs. Two-way ANOVA revealed that the J20 ani- glia activation in the DG subregion was observed in the mals showed significantly better walking performance WBV vs. pseudo-WBV groups (Main effect intervention: compared to the WT animals (Main effect genotype: F = 5.738; p = 0.021) (Fig. 2B). F = 9.410; p = 0.003) (Fig. 1C). In addition, a trend of (1.40) (1.41) Total coverage of CD68 staining, a protein highly improved motor coordination was found in the vibration expressed by activated microglia, was measured in the treated groups compared with pseudo vibration treated same subregions of hippocampus. Representative images animals (vibration treated animals showed decreased of CD68 in the CA1 subregion are visualized in Fig. 2D. walking time on the beam), but it did not reach statisti- Data of the 4 investigated subregions are depicted in cal significance (Fig. 1C). No significant interaction effect Fig. 2E. CD68 coverage in the CA1 region was signifi - of intervention and genotype was observed in the balance cantly decreased by the J20 genotype (main effect geno - beam test. type: F = 6.767; p = 0.012). In addition, a tendency of (1.43) intervention x genotype interaction was also observed Plaque formation (p = 0.06) with a lower coverage in the CA1 region for To determine whether WBV affects the level of amyloid J20-WBV vs. WT pseudo-WBV (post-hoc: 0.07) and deposition in J20 mouse, the total coverage of 6e10 stain- WT-WBV animals (post-hoc: 0.01). Furthermore, a sig- ing was measured in the hippocampus (Hilus, DG, CA3, nificant intervention x genotype effect was found in the and CA1 subregions pooled). An early plaque load was DG subregions (F = 6.999; p = 0.011). Further post- (1.42) found in the hippocampus of J20 mice at the age of six hoc analysis showed a tendency of lower CD68 coverage months. In contrast, plaques were not present in the hip- in the J20-WBV group compared to the J20 pseudo-WBV pocampus of their WT littermates. Furthermore, plaque controls (post-hoc p = 0.08). load was not significantly different between WBV and Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 6 of 12 Fig. 2 Microglia visualized by IBA1 staining in the Hilus subregions is depicted in (A). Eec ff ts of intervention (pseudo vs. WBV ) and genotype ( WT vs. J20) on microglia activation in the CA1, CA3, DG and Hilus subregions are depicted in (B). Significant increase of microglia activation was observed in the J20 animals compared to the WT controls in all subregions (B, CA1, CA3, Dentate Gyrus and Hilus). Microglia activation was only significantly decreased by WBV in the DG (B, Dentate Gyrus). Furthermore, WBV treatment significantly increased the size of microglia dendritic processes in the CA1 and DG subregions (C, CA1 and Dentate Gyrus). Expression of CD68 coverage in the CA1 subregion is visualized in D. Significant decrease of CD68 expression in the CA1 area was detected in the J20 animals compared to the WT controls (E, CA1). In addition, a tendency (p = 0.06) of interaction effect (intervention vs. genotype) on CD68 expression was also observed in the CA1 subregion; additional post-hoc analysis showed a significant decrease for the J20—WBV group compared to the WT—WBV group, as well as the same tendency (p = 0.07) compared to the WT—pseudo WBV group (E, CA1). A significant effect of interaction (intervention vs. genotype) in CD68 expression was observed in the DG area; additional post hoc revealed a strong tendency (p = 0.08) of decrease CD68 expression in the J20—WBV treated animals compared to the J20— pseudo WBV controls (E, Dentate Gyrus). CD68 expression was not significantly altered in the CA3 and Hilus areas (E, CA3 and Hilus). Representative Images of IBA1 and CD68 were taken about the Hilus and CA1 subregions at 200 × magnifications to visualze microglia (A and C). Relevant statistical differences are marked in B, C and D. Data are depicted as mean ± SEM. * indicates: P = .05. Scale bars in A and D are 100 um Astrocytes DG and Hilus hippocampal subregions. Representa- To determine whether hippocampal astrocyte volume tive images of GFAP in the CA3 subregion are visual- would be affected by WBV and/or genotype, covered ized in Fig. 3A. Data of the 4 investigated subregions are area of GFAP positive cells were quantified in CA1, CA3, also summarized in Fig. 3B. Two-way factorial ANOVA Or oszi et al. Behavioral and Brain Functions (2023) 19:5 Page 7 of 12 Table 1 Eec ff ts of intervention (pseudo WBV vs. WBV) and genotype (J20 vs. WT) on microglia number (n), microglia coverage (in %), cell body size and dendrites size measured in pixels, and the number of cells in the CA1, CA3, DG and Hilus subregions of the hippocampus Group Region Microglia number Total coverage (in %) Cell body area (px) Dendrites area (px) (n) Pseudo WBV—WT CA1 33 ± 1.9 16 ± 0.9 237 ± 15 5647 ± 342 CA3 33 ± 2.0 16 ± 1.1 244 ± 12 6094 ± 531 DG 31 ± 1.9 16 ± 0.9 270 ± 16 4993 ± 393 Hilus 25 ± 2.0 15 ± 1.1 262 ± 21 4201 ± 344 Pseudo WBV—J20 CA1 33 ± 1.1 13 ± 0.6 + 353 ± 39 + 5728 ± 332 CA3 32 ± 2.0 13 ± 0.5 + 328 ± 42 + 5734 ± 510 DG 33 ± 1.0 12 ± 0.4 + 365 ± 41 + 4978 ± 277 Hilus 21 ± 1.5 11 ± 0.6 + 398 ± 41 + 3464 ± 214 WBV—WT CA1 36 ± 2.7 16 ± 0.8 257 ± 17 5952 ± 404* CA3 32 ± 1.8 16 ± 0.7 252 ± 14 5948 ± 379 DG 31 ± 1.9 16 ± 0.7 267 ± 14 6129 ± 261* Hilus 21 ± 2.0 14 ± 0.8 271 ± 12 4460 ± 308 WBV—J20 CA1 34 ± 1.9 15 ± 0.7 + 348 ± 45 + 6950 ± 163* CA3 31 ± 1.6 15 ± 0.9 + 349 ± 35 + 6764 ± 355 DG 34 ± 1.6 14 ± 0.7 + 368 ± 43 + 6335 ± 299* Hilus 22 ± 2.7 11 ± 0.7 + 361 ± 42 + 3829 ± 448 Microglia number was not significantly altered by genotype or intervention. Significantly higher coverage was detected in the J20 mice compared to the WT mice in all subregions. In contrast, cell body size was significantly increased in the J20 animals compared to the WT animals. WBV treatment significantly increased the size of dendritic processes in both the J20 and WT mice in the CA1 and DG areas. Data are depicted as mean ± SEM. + indicates a significant difference between the main factors “wild type vs. J20” indicates a significant difference between main factors “WBV vs. pseudo WBV”. Additional figures related to these parameters can be found in the Additional file 1 revealed a significantly lower volume of GFAP positive mice to WBV for five weeks ameliorated the early pro - cells in the CA1 and Hilus subregions of J20 animals gression of astroglial pathology. In contrast, WBV did not compared to their WT littermates (Fig. 3B. Further, influence microglia activation or the amyloid plaque load WBV significantly increased astrocyte coverage in the in the human APP-J20 mouse model. Hilus subregions (F = 20.96; p < 0.001) (Fig. 3B. A A reduction in volume (coverage) of GFAP positive (1.41) genotype x intervention was found in the CA3 subre- astrocytes in the hippocampus was found in J20 vs. WT gion (F = 10.58; p = 0.002). It was found that WT ani- mice including the CA1, DG and Hilus. This is in line (1.39) mals showed lower coverage in WBV vs. pseudo group, with other reports showing a reduction in volume of whereas the J20 animals had higher coverage in WBV vs. GFAP positive astrocytes in J20 mice of 5–6 months of pseudo group. Additional post-hoc analysis revealed that age, however, it was not visible at 8 months indicating the coverage in CA3 region was significantly higher for that astrocyte population may only decrease during the WBV vs. pseudo-WBV in J20 mice (post hoc = 0.023) and early stage of AD pathogenesis [37, 38]. In contrast to it was lower for J20 – pseudo-WBV vs. WT pseudo-WBV these results, a significantly increased coverage of GFAP mice (post-hoc = 0.009) (Fig. 3B). Consistent with these positive astrocytes has been reported in J20 mice at 6 and observations, a similar trend was detected in the CA1 9 months of age [32, 39]. These previously reported find - region, but this interaction effect did not reach statistical ings suggest the presence of an early AD-related deficit; significance. however, certain recovery mechanisms may become acti- vated later on in life. These findings are most likely due to Discussion the complex balance between neurotoxic and neuropro- The aim of this experiment was to investigate the thera - tective effects depending on the disease stage and micro - peutic impact of long-term (five weeks) WBV interven - environmental factors (Rodríguez-Giraldo et al., 2022 tion with low intensity of a sinusoidal nature on amyloid and references therein ). Although WBV did amelio- deposition, neuroinflammation and motor performance rate the astroglial pathological changes in J20 mice, it did during the early stage of AD in hAPP-J20 transgenic not reduce plaque load. This is in line with the findings mice. Our results demonstrated that exposure of J20 from Wang et al. that early activation of astrocytes at the Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 8 of 12 Fig. 3 GFAP + astrocytes in the CA3 hipocampal subregion are visualized in (A). Eec ff ts of intervention (pseudo vs. WBV ) and genotype (J20 vs. WT ) on expression of GFAP positive cells in the CA1, CA3, DG and Hilus regions are depicted in B. Significantly decreased coverage of GFAP positive cells in the J20 animals was detected in the CA1 and Hilus regions (B, CA1 and Hilus). The same trend was observed in the CA3 and Hilus subregions (B, CA3 and Hilus). Significant effect of interaction (intervention vs. genotype) was detected in the CA1 and CA3 subregions (B, CA1 and CA3). Additional posthoc analysis revealed that WT—WBV and pseudo WBV groups showed significantly higher coverage compared to the J20 – pseudo WBV group in the CA1 region (B, CA1). Significantly increased GFAP coverage was detected in the J20—WBV and WT—pseudo WBV groups compared to the J20—pseudo WBV group in the CA3 region (B, CA3). In addition, significant increase of GFAP coverage was detected by WBV in the Hilus region (Panel B, Hilus). Representative images of GFAP + astrocytes were taken about the CA3 hippocampal subregion at 200 × magnifications (A). Data are depicted as mean ± SEM. * indicates: P = .05. ** P < .01. *** P < .001. Scale bars in A are 100 um age of 3–5 months does not influence the deposition of dynamics, muscle strength and motor coordination [17, amyloid plaques in the brains of J20 mice . 22, 23, 34]. Although this neuromuscular response to As far as we know, neither WBV as a form of pas- WBV appears to be a pivotal adaptation, only a trend sive exercise nor active exercise have been investigated of improved motor coordination was found in the pre- regarding hippocampal functioning in the human APP- sent study for both J20 and WT mice. J20 animals out- J20 mouse model. However, another form of cognitive performed the WT littermates in the balance beam test. stimulation, known as enrichment environment, has This is most likely due to the known hyperactivity of the been reported to prevent astroglial volume and mor- J20 mice. Altered locomotor activity such as hyperactiv- phological changes in the early stage of AD in the hip- ity and disturbed home cage activity has been commonly pocampus of J20 mice . Long-term environmental reported in AD mouse models including J20 mice, which enrichment restored the astrocyte parameters similar are often associated with increased amyloid levels and to the age-matched non-transgenic control animals. In disease progression . The onset of these disturbances their design, no exercise devices (for instance: running varies between different models, however, the J20 model wheel or disc) were included to ensure mainly cognitive is one of them that seems to develop disruptions the ear- stimulation by the enrichment environment. In our cur- liest (around 1 month of age) . We hypothesize, that rent study, we demonstrated similar effects that altered the J20 animals approached the upper limit of their per- astrocyte morphology regarding AD progression can be formance due to their disturbed locomotor behavior and reversed by exposure to a long-term WBV intervention. thereby contributed to the mitigation of WBV’s effects on Hence, WBV seems to be able to mimic the effects of motor coordination. In addition, this trend of improved enrichment environment in the early stage of AD in J20 motor performance appears to be more pronounced in animals. the WT animals. This observation seems to be in line One of the mostly emphasized effects of WBV is stimu - with our previous studies reported in young mice  lating and improving the musculoskeletal system. This is and old rats [22, 23]. based on ample clinical and pre-clinical studies [41–43]. We found in earlier studies from our research group In rodents, low-intensity WBV improves neuromuscular that long-term (5 weeks) WBV has broad effects in young Or oszi et al. Behavioral and Brain Functions (2023) 19:5 Page 9 of 12 mice including improvements in motor performance, finding indicates that WBV might be a more beneficial memory functions and levels of neurotransmitters [34, stimulus in the DG to shift microglia towards a more 35, 45]. In contrast, WBV did not influence the body ramified morphology due to amelioration of dendritic weight of the animals in these studies [34, 35, 45]. A pos- processes, such as sensing the surrounding tissue. These sible explanation is that here we used WBV twice per day, discrepancies in the observed parameters might also be instead of once. The extra physical activity that comes related to the relative early stage of the disease. Taken with the handling procedure (for both the WBV and the together, the beneficial effects of WBV on hippocampal pseudo-WBV groups) could account for this finding. microglia activation have been reported recently. Our However, it should be noted that the observed reduction research group found that WBV is able to reduce aging- of body weight over the time course of the intervention related neuroinflammation associated with higher degree is very small and probably biologically irrelevant for the of microglia ramification in 18 months old rats . Our mice. current findings seem to be in line with this observation. In accordance with the literature, we found an early Furthermore, it was reported by others, that long-term plaque load in the hippocampus of J20 mice at the age WBV intervention alleviates increased level of micro- of 6.5 months. Further, the number and volume of amy- glia immunostaining and reversed the decreased level of loid beta plaques seem to be comparable to those that GFAP positive astrocytes in the CA1 hippocampal subre- have been reported in 5–6 months old J20 mice [37, 39]. gions of Sprague–Dawley rats induced by restrain stress Although fewer animals with a relatively high plaque load test . These findings suggest that WBV intervention were observed after WBV, no significant overall reduc - in older J20 mice may yield different results as seen here tion was found. Apparently WBV did not affect plaque in young J20 mice due to increased responsiveness of the load, although studies using ultrasound-based vibrational microglia. alternatives seem to reduce plaque load in various AD The positive impact of WBV on the functioning of models [46–50]. However, it is important to emphasize compromised astrocytes is a novel finding. Tradition - that these experiments do not show unanimity regard- ally, astrocytic pathology is characterized by an increase ing outcome measures and methodical approaches, and in the volume of GFAP-positive astrocytes, most notably direct comparison with WBV is limited. Our results may seen in astrogliosis (see, for review, Kim et al., 2018 and though suggest that the vibratory aspect of ultrasound- references therein ). However, a decrease in the vol- based therapies is not the main causal factor for the ume of hippocampal GFAP-immunoreactive astrocytes observed findings. has been found in relation to depression and mood-disor- There is evidence for the toxicity of amyloid beta ders in human tissue and after posttraumatic stress disor- regarding glial activation including both microglia and der in rats [52, 53]. A decrease in the volume or coverage astrocytes [6–8]. We found significantly increased micro - is most likely caused by a retraction of the astrocytic glia activation (based on morphology and predomi- processes which will cause a decreased participation of nantly an increase in cell body size) in all hippocampal astrocytic end feet in the tripartite synapse . Hence, subregions of J20 animals compared to their WT litter- it could be that this type of astrocytic pathology reduces mates. In contrast, CD68 positive cells only showed an the uptake of excess of synaptic glutamate, leading to increase in the CA1 region. These observed discrepancies increased risk of excitotoxicity as also suggested by oth- between both microglia markers could be related to the ers . Reduced astrocytic functioning due to shrinkage complex early events in the progression of neuroinflam - also negatively affects the release of neurotrophic factors mation. Available data from literature also indicate that . We therefore interpret the decrease of GFAP in our a significantly increased number of activated CD68 and data as a sign of pathology, and the recovery by WBV to IBA1 positive microglia cells was detectable in the hip- the levels as seen in control animals as the prevention of pocampus of J20 mice at 6–9 months of age compared pathology or its reversal if it was already present before to age-matched WT controls [37, 39]. Our findings seem we started the WBV intervention. to be in line with these previously reported observa- Restoring the volume (coverage) of GFAP-positive tions. It was also found that WBV was able to ameliorate astrocytes could promote cellular signaling and synap- microglia activation in both J20 and WT animals in the tic plasticity, functions know to be sensitive to WBV DG subregions. This finding seems to be associated with [20; 45]. Both astrocytes and microglia can modify their increased dendritic processes of microglia in the DG and morphology in response to their direct cellular vinicity CA1 regions. However, despite the same tendency micro- [6–8] and are endowed with receptors for different types glia activation in the CA1 regions was not significantly of neurotrophic factors [55–57] and neurotransmitters altered by WBV treatment. Furthermore, WBV did not . For instance: astrocytes posess TrkB1 receptors, the affect cell body size in all investigated subregions. This binding site of the neurotrophic factor BDNF, as well as Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 10 of 12 cholinergic, serotonergic and dopaminergic receptors. to the J20 (main effect genotype). Whether this difference These findings suggest that these morphological altera - between WT and J20 animals in body weight influenced tions could be mediated through multiple pathways and the efficiency of the WBV treatment is unknown. might be crucial for neural activity, synaptic plasticity and maintenance [58, 59]. It is also known that WBV Recommandations for future research exposure can stimulate the release of various neuro- The initially stated aim of this study was to determine the transmitters in different brain regions including the hip - contextual underlying mechanisms that might contribute pocampus [45, 60, 61], potentially supporting neuronal to the beneficial effects of WBV in the J20 mouse model, activity and health. Similarly, an increased level of BDNF a well-known model for AD. While recognizing the limi- was also detected after long-term vibration interven- tations of this research, we think, that we were able, at tions [21, 25]. Populations of reactive astrocytes local- least in part, to achieve our objectives. We have identi- ized around the senile plaques could be able to produce, fied the involvement of astrocytes in WBV-mediated together with microglia, a wide range of pro-inflamma - effects. These findings can lead to specific outcomes in tory molecules and contribute to the inflammatory state determining the research questions and strategies of . WBV may have the therapeutic potential to mitigate future studies. Based on the available body of literature the level of pro-inflammatory factors after brain damage regarding WBV and AD (as well the J20 mouse model), . This preventive effect of WBV on astroglia volume we concluded that future studies should examine the might also be associated with the mitigation of pro- influence of WBV on cognition and behavior including inflammatory responses. depression, anxiety and memory functions, as well as on further molecular markers related to neurogenesis, syn- Limitations aptic plasticity, growth factors, inflammatory and other Some limitations need to be addressed. Although the neural markers. All of these research objectives could be design of our WBV protocol was chosen and planned relevant future perspectives in relation to AD and WBV. carefully, it required the use of pseudo-control groups to determine the sole effect of the vibrations. The con - Conclusion trol animals underwent pseudo-treatment and may also The results of this study suggest that glial changes in the experience improvements in reducing the progression of early phase of amyloid pathology could be prevented amyloid pathology, as a result of the exposure to a new by chronic (five weeks) exposure to low-intensity WBV. environment (i.e. the compartments of the vibration Our results contribute to the understanding of glial plas- plate). ticity in response to WBV, which can be considered a A significant decline of body weight was detected dur - new, potential therapeutic approach for neurodegenera- ing the first two weeks of the intervention in the WT tive diseases. The clinical relevance has yet to be deter - animals, but not in the J20 animals (time course * geno- mined, and may be restricted to the early phase of AD as type). Further, a strong tendency of lower body weight we found that WBV in late phase AD patients could not was explored in the WBV treated group (main factor: improve their cognitive performance, despite the demon- intervention), however, the interaction of time course strated feasibility of WBV for (fragile) AD patients . and intervention was not significantly altered (time Our results seem to be consistent with the existing litera- course * intervention). Although the animals underwent ture and indicate that glial cells can respond to vibrational prior habituation to the experimental room and its con- stimuli adopting their volume to the condition as was ditions before the start of the intervention, this indicates found in the control mice. The underlying mechanism(s) that the WT animals might have experienced some dis- could implicate parallel molecular and cellular responses comfort or stress or have been more sensitive during the such as altered energy metabolism, recycling and/or first two weeks of the intervention. Over the last years, release of neurotransmitters and neurotrophic factors, we have not experienced this kind of fluctuation in body especially in the plastic brain areas like the hippocampus. weight in mice or rats in our former experiments [22, Whether these mechanisms indeed play a key role has to 23, 34, 35, 45]. Also, neither WBV nor pseudo WBV did be determined in future studies. Further, the understand- influence the body weight of mice in our previous works ing and unraveling of these underlying mechanisms by with the same WBV device and settings [34, 35, 45]. We translational scientific investigations can contribute to made the same observations in rats [22, 23]. This minor more advanced and effective study procedures and WBV decline in body weight only in WT mice indicates that protocols as indicated earlier by our research group . modifications in habituation and handling procedures In conclusion, the possibility that the progression of may be considered in future projects. Finally, the WT derailing of microglial and astroglial activation such as animals had significantly higher body weights compared seen in neuroinflammation in the early stage of AD (and Or oszi et al. Behavioral and Brain Functions (2023) 19:5 Page 11 of 12 2. Fakhoury M. Microglia and astrocytes in Alzheimer’s disease: implications most likely other types of neurodegenerative diseases) for therapy. Curr Neuropharmacol. 2018;16:508–18. can be slowed by application of WBV, as a passive alter- 3. Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer’s disease. J Cell native for active exercise, puts forward WBV as a treat- Biol. 2018;217:459–72. 4. Matsuoka Y, Picciano M, Malester B, LaFrancois J, Zehr C, Daeschner JM, ment strategy worthwhile to pursuit. Notably for those et al. Inflammatory responses to amyloidosis in a transgenic mouse unable to participate in active exercise protocols. model of Alzheimer’s disease. Am J Pathol. 2001;158:1345–54. 5. Ries M, Sastre M. Mechanisms of Aβ clearance and degradation by glial cells. Front Aging Neurosci. 2016. https:// doi. org/ 10. 3389/ fnagi. 2016. Supplementary Information The online version contains supplementary material available at https:// doi. 6. Solito E, Sastre M. Microglia function in Alzheimer’s disease. Front org/ 10. 1186/ s12993- 023- 00208-9. Pharmacol. 2012. https:// doi. org/ 10. 3389/ fphar. 2012. 00014. 7. Lee CYD, Landreth GE. The role of microglia in amyloid clearance from Additional file 1: Figure S1. Eec ff ts of genotype x time course (panel A) the AD brain. J Neural Transm. 2010;117:949–60. and time course (panel B) were observed on body weight. Body weight 8. Rodríguez JJ, Olabarria M, Chvatal A, Verkhratsky A. Astroglia in demen- was significantly decreased from week 1 - 2 to week 3 – 6 in the wild type tia and Alzheimer’s disease. Cell Death Differ. 2009;16:378–85. animals. In contrast, this effect was not observed in the J20 animals. Sig- 9. Mendiola-Precoma J, Berumen LC, Padilla K, Garcia-Alcocer G. Thera- nificant decrease of body weight (effect of tiem course) was also revealed pies for prevention and treatment of Alzheimer’s disease. Biomed Res on week 1 vs. week 3, 5 and 6. Int. 2016;2016:1–17. 10. Vaz M, Silvestre S. Alzheimer’s disease: recent treatment strategies. Eur J Pharmacol. 2020;887:173554. Acknowledgements 11. Sanders LMJ, Hortobágyi T, la Bastide-van GS, van der Zee EA, van We thank our technicians Kunja Slopsema and Jan Keijser for their excellent Heuvelen MJG. Dose-response relationship between exercise and cog- assistance with immunostainings and image analyses. nitive function in older adults with and without cognitive impairment: a systematic review and meta-analysis. PLoS ONE. 2019;14:e0210036. Author contributions 12. Jahangiri Z, Gholamnezhad Z, Hosseini M. Neuroprotective effects of EZ made the conception and the design of the study. EZ and MH contributed exercise in rodent models of memory deficit and Alzheimer’s. Metab to the acquisition of financial support leading to this publication. OT per - Brain Dis. 2019;34:21–37. formed part of the animal experiment and the stainings; organized the data 13. De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador- and did the statistical analysis; and wrote the first draft of the manuscript. EG Pascual A, García-Lucerga C, et al. Physical exercise in the prevention and RR assisted with the animal experiment and immunostainings. All authors and treatment of Alzheimer’s disease. J Sport Heal Sci. 2020;9:394–404. read and approved the final manuscript. 14. Rodríguez-Giraldo M, González-Reyes RE, Ramírez-Guerrero S, Bonilla- Trilleras CE, Guardo-Maya S, Nava-Mesa MO. Astrocytes as a therapeu- Funding tic target in alzheimer’s disease–comprehensive review and recent Open access funding provided by Hungarian University of Sports Science. This developments. Int J Mol Sci. 2022;23:13630. study was partly supported by ZonMW, Deltaplan Dementia and Alzheimer 15. Runge M, Rehfeld G, Resnicek E. Balance training and exercise in geriat- Nederland and Brain Foundation (Memorabel, 733050303). ric patients. J Musculoskelet Neuronal Interact. 2000;1:61–5. 16. Zhang L, Weng C, Liu M, Wang Q, Liu L, He Y. Eec ff t of whole-body Availability of data and materials vibration exercise on mobility, balance ability and general health status The dataset(s) supporting the conclusions of this article is(are) included within in frail elderly patients: a pilot randomized controlled trial. Clin Rehabil. the article (and its Additional File 1). 2014;28:59–68. 17. Mettlach G, Polo-Parada L, Peca L, Rubin CT, Plattner F, Bibb JA. Enhancement of neuromuscular dynamics and strength behavior Declarations using extremely low magnitude mechanical signals in mice. J Biomech. 2014;47:162–7. Ethics approval and consent to participate 18. Patel VS, Chan ME, Pagnotti GM, Frechette DM, Rubin J, Rubin CT. The animal study was reviewed and approved by the national Competent Incorporating refractory period in mechanical stimulation mitigates Authority (CCD) and the local ethical committee (DierExperimentenCommis- obesity-induced adipose tissue dysfunction in adult mice. Obesity. sie) of the University of Groningen, The Netherlands. 2017;25:1745–53. 19. Corbiere T, Weinheimer-Haus E, Judex S, Koh T. Low-intensity vibration Competing interests improves muscle healing in a mouse model of laceration injury. J Funct The authors declare that they have no competing interests. Morphol Kinesiol. 2017;3:1. 20. Cariati I, Bonanni R, Pallone G, Annino G, Tancredi V, D’Arcangelo G. Author details Modulation of synaptic plasticity by vibratory training in young and Department of Neurobiology, Groningen Institute for Evolutionary Life Sci- old mice. Brain Sci. 2021;11:82. ences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG Groningen, 21. Peng G, Yang L, Wu CY, Zhang LL, Wu CY, Li F, et al. Whole body The Netherlands. Research Center for Molecular Exercise Science, Hungarian vibration training improves depression-like behaviors in a rat chronic University of Sports Science, Budapest, Hungary. Department of Morphology restraint stress model. Neurochem Int. 2021;142:104926. and Physiology, Health Science Faculty, Semmelweis Univesity, Budapest, Hun- 22. Oroszi T, Geerts E, de Boer SF, Schoemaker RG, van der Zee EA, Nyakas gary. Department of Human Movement Sciences, University of Groningen, C. Whole body vibration improves spatial memory, anxiety-like behav- University Medical Center Groningen, Groningen, The Netherlands. ior, and motor performance in aged male and female rats. Front Aging Neurosci. 2022. https:// doi. org/ 10. 3389/ fnagi. 2021. 801828. Received: 28 September 2022 Accepted: 2 March 2023 23. Oroszi T, de Boer SF, Nyakas C, Schoemaker RG, van der Zee EA. Chronic whole body vibration ameliorates hippocampal neuroinflammation, anxiety-like behavior, memory functions and motor performance in aged male rats dose dependently. Sci Rep. 2022;12:9020. 24. Huang D, Yang Z, Wang Z, Wang P, Qu Y. The macroscopic and micro- References scopic effect of low-frequency whole-body vibration after cerebral 1. Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: ischemia in rats. Metab Brain Dis. 2018;33:15–25. causes and treatment. Molecules. 2020;25:5789. 25. Raval A, Schatz M, Bhattacharya P, d’Adesky N, Rundek T, Dietrich W, et al. Whole body vibration therapy after ischemia reduces brain Oroszi et al. Behavioral and Brain Functions (2023) 19:5 Page 12 of 12 damage in reproductively senescent female rats. Int J Mol Sci. 46. Bobola MS, Chen L, Ezeokeke CK, Olmstead TA, Nguyen C, Sahota A, et al. 2018;19:2749. Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia 26. Monteiro F, Sotiropoulos I, Carvalho Ó, Sousa N, Silva FS. Multi-mechanical acutely and reduces Aβ load chronically, as demonstrated in vivo. Brain waves against Alzheimer’s disease pathology: a systematic review. Transl Stimul. 2020;13:1014–23. Neurodegener. 2021;10:36. 47. Leinenga G, Götz J. Safety and efficacy of scanning ultrasound treatment 27. Mucke L, Masliah E, Yu G-Q, Mallory M, Rockenstein EM, Tatsuno G, et al. of aged APP23 mice. Front Neurosci. 2018;12:55. High-level neuronal expression of Aβ in wild-type human amyloid 48. D’Haese P-F, Ranjan M, Song A, Haut MW, Carpenter J, Dieb G, et al. 1–42 protein precursor transgenic mice: synaptotoxicity without plaque forma- β-Amyloid plaque reduction in the hippocampus after focused tion. J Neurosci. 2000;20:4050–8. ultrasound-induced blood-brain barrier opening in Alzheimer’s disease. 28. Harris JA, Devidze N, Halabisky B, Lo I, Thwin MT, Yu G-Q, et al. Many Front Hum Neurosci. 2020;14:593672. neuronal and behavioral impairments in transgenic mouse models of 49. Jordão JF, Thévenot E, Markham-Coultes K, Scarcelli T, Weng Y-Q, Xhima Alzheimer’s disease are independent of caspase cleavage of the amyloid K, et al. Amyloid-β plaque reduction, endogenous antibody delivery and precursor protein. J Neurosci. 2010;30:372–81. glial activation by brain-targeted, transcranial focused ultrasound. Exp 29. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, et al. ABAD Neurol. 2013;248:16–29. Directly links Aß to mitochondrial toxicity in Alzheimer’s disease. Science. 50. Poon CT, Shah K, Lin C, Tse R, Kim KK, Mooney S, et al. Time course 2004;304:448–52. of focused ultrasound effects on β-amyloid plaque pathology in the 30. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, TgCRND8 mouse model of Alzheimer’s disease. Sci Rep. 2018;8:14061. et al. Accelerating amyloid-β fibrillization reduces oligomer levels and 51. Kim R, Healey KL, Sepulveda-Orengo MT, Reissner KJ. Astroglial correlates functional deficits in Alzheimer disease mouse models. J Biol Chem. of neuropsychiatric disease: from astrocytopathy to astrogliosis. Prog 2007;282:23818–28. Neuropsychopharmacol Biol Psychiatry. 2018;87:126–46. 31. Lalonde R, Kim HD, Fukuchi K. Exploratory activity, anxiety, and motor 52. Saur L, Baptista PP, Bagatini PB, Neves LT, de Oliveira RM, Vaz SP, et al. coordination in bigenic APPswe + PS1/ΔE9 mice. Neurosci Lett. Experimental post-traumatic stress disorder decreases astrocyte density 2004;369:156–61. and changes astrocytic polarity in the CA1 hippocampus of male rats. 32. Wright AL, Zinn R, Hohensinn B, Konen LM, Beynon SB, Tan RP, et al. Neu- Neurochem Res. 2015;41:892–904. roinflammation and neuronal loss precede Aβ plaque deposition in the 53. Cobb JA, O’Neill K, Milner J, Mahajan GJ, Lawrence TJ, May WL, et al. Den- hAPP-J20 mouse model of Alzheimer’s disease. PLoS ONE. 2013;8:e59586. sity of GFAP-immunoreactive astrocytes is decreased in left hippocampi 33. van Heuvelen MJG, Rittweger J, Judex S, Sañudo B, Seixas A, Fuermaier in major depressive disorder. Neuroscience. 2016;316:209–20. ABM, et al. Reporting guidelines for whole-body vibration studies in 54. González-Reyes RE, Nava-Mesa MO, Vargas-Sánchez K, Ariza-Salamanca humans, animals and cell cultures: a consensus statement from an inter- D, Mora-Muñoz L. Involvement of astrocytes in alzheimer’s disease from a national group of experts. Biology. 2021;10:965. neuroinflammatory and oxidative stress perspective. Front Mol Neurosci. 34. Keijser JN, Marieke JG, van Heuvelen MJG, Nyakas C, Toth K, Schoemaker 2017. https:// doi. org/ 10. 3389/ fnmol. 2017. 00427. RG, et al. Whole body vibration improves attention and motor perfor- 55. Ohira K, Funatsu N, Homma KJ, Sahara Y, Hayashi M, Kaneko T, et al. Trun- mance in mice depending on the duration of the whole body vibration cated TrkB-T1 regulates the morphology of neocortical layer I astrocytes session. African J Tradit Complement Altern Med. 2017;14:128–34. in adult rat brain slices. Eur J Neurosci. 2007;25:406–16. 35. Boerema AS, Heesterbeek M, Boersma SA, Schoemaker R, de Vries 56. Condorelli DF, Salin T, Dell’Albani P, Mudò G, Corsaro M, Timmusk T, et al. EFJ, van Heuvelen MJG, et al. Beneficial effects of whole body vibra- Neurotrophins and theirtrk receptors in cultured cells of the glial line- tion on brain functions in mice and humans. Dose Response. age and in white matter of the central nervous system. J Mol Neurosci. 2018;16:155932581881175. 1995;6:237–48. 36. Hovens I, Nyakas C, Schoemaker R. A novel method for evaluating micro- 57. Soontornniyomkij V, Wang G, Pittman CA, Hamilton RL, Wiley CA, Achim glial activation using ionized calcium-binding adaptor protein-1 staining: CL. Absence of brain-derived neurotrophic factor and trkB receptor cell body to cell size ratio. Neuroimmunol Neuroinflamm. 2014;1:82. immunoreactivity in glia of Alzheimer’s disease. Acta Neuropathol. 37. Beauquis J, Pavía P, Pomilio C, Vinuesa A, Podlutskaya N, Galvan V, et al. 1999;98:345–8. Environmental enrichment prevents astroglial pathological changes in 58. Murphy S, Pearce B. Functional receptors for neurotransmitters on astro- the hippocampus of APP transgenic mice, model of Alzheimer’s disease. glial cells. Neuroscience. 1987;22:381–94. Exp Neurol. 2013;239:28–37. 59. Benediktsson AM, Schachtele SJ, Green SH, Dailey ME. Ballistic labeling 38. Fu Y, Rusznák Z, Kwok JBJ, Kim WS, Paxinos G. Age-dependent alterations and dynamic imaging of astrocytes in organotypic hippocampal slice of the hippocampal cell composition and proliferative potential in the cultures. J Neurosci Methods. 2005;141:41–53. hAβPPSwInd-J20 mouse. J Alzheimer Dis. 2014;41:1177–92. 60. Zhao L, He LX, Huang SN, Gong LJ, Li L, Lv YY, et al. Protection of dopa- 39. Ameen-Ali KE, Simpson JE, Wharton SB, Heath PR, Sharp PS, Brezzo G, mine neurons by vibration training and up-regulation of brain-derived et al. The time course of recognition memory impairment and glial neurotrophic factor in a MPTP mouse model of Parkinson’s disease. pathology in the hAPP-J20 mouse model of Alzheimer’s disease. J Alzhei- Physiol Res. 2014. https:// doi. org/ 10. 33549/ physi olres. 932743. mer Dis. 2019;68:609–24. 61. Ariizumi M, Okada A. Eec ff ts of whole body vibration on biogenic amines 40. Wang D, Zhang X, Wang M, Zhou D, Pan H, Shu Q, et al. Early activation in rat brain. Occup Environ Med. 1985;42:133–6. of astrocytes does not affect amyloid plaque load in an animal model of 62. Krause DL, Müller N. Neuroinflammation, microglia and implications for Alzheimer’s disease. Neurosci Bull. 2018;34:912–20. anti-inflammatory treatment in Alzheimer’s disease. Int J Alzheimer Dis. 41. Alam MM, Khan AA, Farooq M. Eec ff t of whole-body vibration on neuro - 2010;2010:1–9. muscular performance: a literature review. Work. 2018;59:571–83. 63. Heesterbeek M, van der Zee EA, van Heuvelen MJG. Feasibility of three 42. Savage R, Billing D, Furnell A, Netto K, Aisbett B. Whole-body vibration novel forms of passive exercise in a multisensory environment in and occupational physical performance: a review. Int Arch Occup Environ vulnerable institutionalized older adults with dementia. J Alzheimer Dis. Health. 2016;89:181–97. 2019;70:681–90. 43. Prisby RD, Lafage-Proust M-H, Malaval L, Belli A, Vico L. Eec ff ts of whole 64. Oroszi T, van Heuvelen MJG, Nyakas C, van der Zee EA. Vibration detec- body vibration on the skeleton and other organ systems in man and tion: its function and recent advances in medical applications. F1000 animal models: What we know and what we need to know. Ageing Res Research. 2020;9:619. Rev. 2008;7:319–29. 44. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. Using Publisher’s Note mice to model Alzheimer’s dementia: an overview of the clinical disease Springer Nature remains neutral with regard to jurisdictional claims in pub- and the preclinical behavioral changes in 10 mouse models. Front Genet. lished maps and institutional affiliations. 2014. https:// doi. org/ 10. 3389/ fgene. 2014. 00088. 45. Heesterbeek M, Jentsch M, Roemers P, Keijser JN, Toth K, Nyakas C, et al. Whole body vibration enhances choline acetyltransferase-immunoreac- tivity in cortex and amygdala. J Neurol Transl Neurosci. 2017;5(2):1079.
Behavioral and Brain Functions – Springer Journals
Published: Mar 20, 2023
Keywords: Passive exercise; Neuroinflammation; Amyloid beta; J20 mice; Motor coordination
Access the full text.
Sign up today, get DeepDyve free for 14 days.