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- Springer Journals
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- 2018 The Author(s)
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- 1744-9081
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- 10.1186/s12993-018-0144-9
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Abstract
Background: Predatory stress as a psychological stressor can elicit the activation of the hypothalamic–pituitary– adrenal (HPA) axis, which is involved in the dialogue of the neuroimmunoendocrine network. The brain has been proven to regulate the activity of the HPA axis by way of lateralization. In the present study, we probed the pivotal ele‑ ments of the HPA circuitry including CRH, GR and a multifunctional cytokine in behavior‑ lateralized mice to determine their changes when the animals were subjected to predator exposure. Methods: Behavior‑ lateralized mice were classified into left ‑ pawed and right‑ pawed mice through a paw‑ preference test. Thereafter, mice in the acute stress group received a single 60‑ min cat exposure, and mice in the chronic group received daily 60‑ min cat exposure for 14 consecutive days. The plasma CS and TNF‑ α were determined by ELISA, the hypothalamic CRH mRNA and hippocampal GR mRNA were detected by real‑ time PCR, and the hippocampal GR protein was detected by western blot analysis. Results: The results revealed that the levels of plasma CS were significantly elevated after chronic predatory expo ‑ sure in both right‑ pawed and left‑ pawed mice; the right‑ pawed mice exhibited a higher plasma CS level than the left‑ pawed mice. Similarly, the acute or chronic cat exposure could induce the release of plasma TNF‑ α, and the left‑ pawed mice tended to show a higher level after the acute stress. Chronic stress significantly upregulated the expres‑ sion of hypothalamic CRH mRNA in both left‑ pawed and right‑ pawed mice. Normally, the left‑ pawed mice exhibited a higher GR expression in the hippocampus than the right‑ pawed mice. After the cat exposure, the expression of GR in both left‑ pawed and right‑ pawed mice was revealed to be greatly downregulated. Conclusion: Our findings indicate that predatory stress can invoke a differential response of stressful elements in behavior‑ lateralized mice. Some of these responses shaped by behavioral lateralization might be helpful for facilitat‑ ing adaption to various stimuli. Keywords: Predator, Stress, Behavior lateralization, HPA, Neuromodulation *Correspondence: zefengxie@sina.com; ksli@stu.edu.cn; yunsu112001@yahoo.com Jiacai Yang and Lin Zhang contributed equally to this work as first authors Ze‑ feng Xie, Kang‑ sheng Li and Yun Su contributed equally to this work Department of Microbiology & Immunology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, People’s Republic of China Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. Yang et al. Behav Brain Funct (2018) 14:12 Page 2 of 8 mice [19, 20]. The normal left-pawed BALB/c mice had Background higher plasma levels of IL-1 than the right-pawed mice. The nature and course of stress can influence an indi - Additionally, male BALB/c mice displayed a link between vidual’s ability to cope with life events, which might turning preference with host against Listeria monocy- result in various consequences [1–4]. Predatory expo- togenes and especially with the production of IL-6 and sure (exposing rodents to a non-attacking predator or interferon-gamma (IFN-Ɣ) [19, 20]. Besides, as for the to the predator’s odors) is a commonly used psychologi- stress system, responses including the activation of HPA cal stressor, triggering effects that are similar to human axis, secretion of glucocorticoids and cytokines from stress-linked phenomena [5–7]. Resembling most types the cortex, hypothalamus and hippocampus, have been of stimuli, predatory stress elicits increased activity of proven to exhibit great differences in behavior asymmet - the hypothalamic–pituitary–adrenal (HPA) axis, which ric groups under physiological conditions, LPS-treatment is involved in the dialogue of neuroimmunoendocrine or stressful conditions [21, 22]. The involved mediators networks. The activity of the HPA axis is modulated by above even showed a correspondence with the direction a series of elements in the central loop such as cortico- and intensity of behavioral lateralization [22]. The activ - tropin releasing hormone (CRH), adrenocorticotrophic ity of the HPA axis is governed by key elements of stress hormone (ACTH) and glucocorticoids [8]. Among these, circuitry in the crosstalk of the neuroimmunoendocrine CRH, which has been predominantly detected in the par- network. Although the brain could modulate HPA activ- aventricular nucleus (PVN) of the hypothalamus, plays a ity asymmetrically, resulting in various alterations in potent role in regulating psycho-immunology and behav- corticosterone (CS) levels for the left-handed/left-pawed ioral effects to stimuli [9]. Normally, a stressful state and right-handed/right-pawed groups, it remains unclear might trigger the secretion of CRH from the hypothala- whether the key elements of HPA circuitry are involved mus; in turn, CRH activates the release of ACTH from in the regulation of behavior lateralization in response to the pituitary and finally stimulates the release of gluco - psychological stressors. Hence, in the present study, we corticoids from the adrenal cortex. In the circuitry, glu- probed the pivotal elements of HPA circuitry including cocorticoids are the final effectors to stressful reactions the CRH, GR and a multifunctional cytokine in behavior- [10, 11]. When binding to the glucocorticoid receptor lateralized mice, to determine their changes when the (GR) [12, 13], glucocorticoids trigger suppressive effects animals were subjected to predator exposure. on the release of various inflammation-related chemical mediators such as TNF-α [14]. The related effects stated Methods above can also be regulated through hippocampal struc- Animals tures. As a facilitator in the stress loop, changes in the Female BALB/cAnN mice (4 weeks old) were used in GR would presumably exert effects on the body’s neuro - our studies. Two short-haired male cats (6 months old; immunoendocrine function. Therefore, all stressful ele - body weight 1.7 and 2.0 kg) were utilized as the predator ments in the circuitry orchestrate and regulate the basal stimulus. The mice and the cats were adapted to the envi - activity of the HPA axis to maintain homeostasis. ronment before any behavioral experiments. All efforts Ascertained by many experiments, the brain modulates were taken to minimize the number of animals and their neurochemical and functional activity through lateraliza- suffering. All animal experiments were approved by the tion. The asymmetric brain is thought to be responsible Animal Care and Use Committee of Shantou University for the differences of certain cognitive and motor tasks. Medical College and were carried out in compliance with Behavioral lateralization, which reflects functional brain the National Institutes of Health Guide for the Care and asymmetry, is a commonly-existing phenomenon. Recent Use of Laboratory Animals. research provides evidences for communication between brain lateralization and the immune system. A good case Behavior lateralization test is that brain lateralized-animals exhibit various responses The paw-preference test was used for the classification to environmental stimuli at both the individual level of the behavior-lateralized animals [19]. The mice were and the population level. In mice, based on paw prefer- deprived of food for 18 h overnight and were then kept ence model as an index of asymmetry, it has been con- in a testing cubicle with a feeding tube. The mice could firmed that there were notable relationships between reach a pellet of food only with the use of one paw. The immune parameters and behavioral lateralization. The numbers of right-paw entries (RPE) per 50 paw reaches immune parameters including natural killer cell activity, to reach the food pellet were scored. Over a 2-week cytotoxic T lymphocyte activity, mitogen-induced lym- period, the mice were tested for four sessions. Based on phoproliferation show an association with paw prefer- the RPE score, the animals were classified as left-pawed ence [15–18]. The plasma levels of IL-1 and IL-6 are also mice if the RPE score was equal to or less than 20 or were different in various strains of left-pawed and right-pawed Yang et al. Behav Brain Funct (2018) 14:12 Page 3 of 8 classified as right-pawed mice if the RPE score was equal was chosen as the calibrator for normalization. Changes to or above 30. Twenty-four right-pawed and 24 left- in relative expression of CRH mRNA and GR mRNA pawed mice were used in our experiments. were evaluated as sample/normal control. Predatory stress procedures Western blotting The right-pawed and left-pawed mice were divided into The total protein concentration was determined using the unstressed control group (normal control group), the BCA protein assay kit (Beyotime, China). The protein acute stress group and chronic stress group (each group samples were subjected to electrophoresis via SDS-PAGE was composed of eight mice). The acute stress group and were transferred onto a PVDF membrane (Roche, received a single 60-min cat exposure, and the chronic UK) using a blot system, according to standard protocols. stress group received daily 60-min cat exposure for 14 Antibodies against GR (Santa Cruz, USA) and β-actin consecutive days. The cat-exposed mice were first placed (Beyotime, China) and a secondary antibody conjugated into a small cage, which allowed for the mice to have to horseradish peroxidase (Beyotime, China) were used access to the visual, olfactory, and acoustic stimuli associ- for image detection. The images were visualized by West - ated with the cats but prohibited physical interaction or ern Blotting Luminol Reagent (Santa Cruz, USA) via Gel a real attack. Next, the cage was placed in a larger com- Imaging System (Alpha Innotech, US). The band intensity partment with the cats. Observation was conducted from was determined using the ImageJ software. The relative outside the room without interference. After completing ratio (GR/β-actin) was calculated. the cat test, all mice were sacrificed by rapid decapitation. Trunk blood samples and the hippocampus and hypo- Statistical analyses thalamus of the brain were collected quickly and stored An analysis of variance (ANOVA) was performed after for further processing. verifying a normal distribution of data and the equality of variances. Log transformation or square root transforma- Detection of CS and TNF‑α tion was performed when the normal test failed. The levels of plasma CS and TNF-α were detected via the In the presence of behavioral lateralization in mice: sta- enzyme-linked immunosorbent assay (CS, TNF-α ELISA tistical analysis of the CS and TNF-α levels in the plasma, kits, BD, USA). All procedures were performed according the CRH mRNA expression in the hypothalamus, and to the manufacturer’s protocols. GR expression in the hippocampus was conducted by two-way ANOVA with stress as a between-groups factor Real‑time PCR (three levels: normal control, acute stress, and chronic The total RNA from the hippocampus and hypothala - stress) and behavioral lateralization as a between-groups mus was extracted using TR Izol reagent (Invitrogen, factor (two levels: left-pawed and right-pawed). This was USA). For the synthesis of cDNA, the total RNA was followed by the post hoc test (Bonferroni correction). reversely transcribed using Moloney murine leukemia The t-test was used to analyze differences between the virus reverse transcriptase (Invitrogen, USA). For quanti- right-pawed and left-pawed mice in each group. tative real-time PCR, SYBR Green Supermix (Invitrogen, In the absence of behavioral lateralization in mice: USA) was used for the detection of the CRH mRNA and the data regarding the plasma CS and TNF levels, the GR mRNA. The sequences of primers specific for CRH, hypothalamic expression of the CRH mRNA, and the GR and glyceraldehyde-3-phosphate dehydrogenase hippocampal expression of the GR were analyzed by (GAPDH) were listed as follows (Table 1). All reactions one-way ANOVA with stress as a between-groups factor were performed in triplicate. ABI Prism7300 was applied with 3 levels (normal control, acute stress, and chronic for analysis. GAPDH was used as the endogenous refer- stress). The post hoc test (Bonferroni test) was per - ence gene. Each sample for CRH and GR gene was calcu- formed to determine the difference between each group −∆∆Ct lated using the 2 method. The normal control group when the stress effect was found. A t-test was performed (not considering the effects of the behavior lateralization) to analyze the differences between the right-pawed and Table 1 Specific primers used in real-time PCR analysis Gene Forward Reverse CRH 5′CAC CTA CCA AGG GAG GAG AA 3′ 5′CAG AGC CAC CAG CAG CAT 3′ GR 5′ATG GGC AAA GGC GAT ACC AGG ATT 3′ 5′CCA ACC CAG GGC AAA TGC CATGA 3 GAPDH 5′GTG ACT TCA ACA GCA ACT CCC ATT 3′ 5′GTT ATG GGG TCT GGG ATG GAA TTG TG3′ Yang et al. Behav Brain Funct (2018) 14:12 Page 4 of 8 left-pawed mice. Statistical analysis was performed by level were elevated after chronic predatory exposure, using SPSS 19.0 and Microsoft Excel software. The data exhibiting a higher level than that in the normal control were expressed as the mean ± SEM. A P value < 0.05 was (P < 0.001) and acute stress groups (P < 0.001) (Fig. 1a). considered statistically significant. When the effect of behavioral lateralization was consid - ered, the CS level increased after chronic predatory stress Results in both right-pawed and left-pawed mice (Fig. 1b). The The levels of plasma CS in behavior‑lateralized mice right-pawed mice exhibited a higher plasma CS concen- after predatory exposure tration than the left-pawed mice after acute (P < 0.001) Figure 1 shows the plasma CS level in behavior-lat- and chronic stress (P < 0.001). eralized mice after predatory exposure. A two-way ANOVA revealed a significant predatory stress effect The levels of plasma TNF‑α in behavior‑lateralized mice [F(2,42) = 86.26; P < 0.001], a brain lateralization effect after predatory exposure [F(1,42) = 47.11; P < 0.001], and a stress × lateralization The levels of plasma TNF-α are shown in Fig. 2. The interaction [F(2,42) = 10.56; P < 0.01]. The plasma CS analysis demonstrated a significant effect of predatory Fig. 1 The levels of plasma CS in behavior‑lateralized mice after predatory stress (8 mice in each group). a Influence of predator exposure on plasma CS. The chronic predatory stress increased the plasma CS to a higher extent than that in the control and acute stress groups (*P < 0.05, **P < 0.01, ***P < 0.001). b Plasma CS in behavior‑lateralized mice with predatory stress. The right ‑pawed mice showed a higher plasma CS concentration than the left‑pawed mice after acute stress and chronic stress. Significant differences were observed between the left ‑pawed and right‑pawed mice in each group (t‑test) (*P < 0.05, **P < 0.01, ***P < 0.001) Fig. 2 The levels of plasma TNF‑α in behavior ‑lateralized mice after predatory stress (8 mice in each group). a Influence of predator exposure on plasma TNF‑α. The TNF‑α level of the acute and chronic stress groups were significantly elevated (*P < 0.05, **P < 0.01, ***P < 0.001). b Plasma TNF‑α in behavior‑lateralized mice with predatory stress. The left ‑pawed and right ‑pawed mice showed significantly elevated TNF‑α levels after acute and chronic predatory stress (*P < 0.05, **P < 0.01, ***P < 0.001) Yang et al. Behav Brain Funct (2018) 14:12 Page 5 of 8 stress groups (left-pawed: chronic stress vs acute stress, stress [F(2,42) = 197.13; P < 0.001] but no effects of P = 0.022; right-pawed: chronic stress vs acute stress, behavioral lateralization [F(1,42) = 3.50; P = 0.068] P < 0.001) (Fig . 3b). and stress × lateralization interaction [F(2,42) = 0.934; P = 0.401]. One-way ANOVA revealed that the TNF-α levels were significantly elevated in the acute (P < 0.001) The expression of GR in the hippocampus and chronic stress groups (P < 0.001) (Fig. 2a), especially of behavior‑lateralized mice after predatory exposure in the chronic stress mice. The left-pawed and right- For the GR mRNA, one-way ANOVA demonstrated pawed mice showed increased TNF-α levels after acute that acute and chronic predatory stress could downreg- stress (P < 0.001) and chronic stress (P < 0.001) (Fig. 2b). ulate the expression after acute (P < 0.001) and chronic The left-pawed mice tended to exhibit higher levels of stress (P < 0.001) (Fig . 4a). Two-way ANOVA showed TNF-α than the right-pawed mice after acute (P = 0.12) a predatory stress effect [F (2,42) = 59.04, P < 0.001], a and chronic stress (P = 0.099); however, no significant brain lateralization effect [F (1,42) = 12.45, P = 0.002], differences were observed. and a stress × lateralization interaction [F(2,42) = 17.71, P < 0.001] in the left hippocampus. Similarly, a preda- The expression of CRH mRNA in the hypothalamus tory stress effect [F (2,42) = 43.17, P < 0.001], a brain of behavior‑lateralized mice after predator exposure lateralization effect [F (1,42) = 21.04, P < 0.001], and Considering stress and behavioral lateralization (right- a stress × lateralization interaction [F(2,42) = 16.42, pawed and left-pawed) as factors, two-way ANOVA P < 0.001] were also found in the right hippocampus. showed only a stress effect [F (2,42) = 28.75, P < 0.001] The data showed that the normal control group exhib - and stress × lateralization interaction [F(2,42) = 4.417; ited a higher expression of the GR mRNA in the left P = 0.023], but no lateralization effect [F (1,42) = 0.90, (P < 0.001) and right hippocampus (P < 0.001) of the left- P = 0.351] on the expression of the CRH mRNA in the pawed mice than that in the right-pawed mice (Fig. 4b, hypothalamus. Considering the normal control group c). After stress, the expression of GR in the left-pawed as the calibrator, our real-time PCR data revealed that mice was downregulated more profoundly than that in the chronic predator stress increased the expression the right-pawed mice. Western blot analysis revealed of the CRH mRNA when compared with the control that the changes in the GR protein were similar to those group (P < 0.001) and the acute stress group (P < 0.001) in the GR mRNA expression when considering stress as (Fig. 3a). Both in the left-pawed and right-pawed mice, a factor. The expression of the GR protein was reduced the expression of CRH mRNA was profoundly elevated both in the left and right hippocampal formation of after chronic stress, when compared with the control the acute (P < 0.05) and chronic stress groups (P < 0.05) (left-pawed: chronic stress vs control, P = 0.035; right- (Fig. 4d–h). pawed: chronic stress vs control, P < 0.001) and acute Fig. 3 The expression of CRH mRNA in the hypothalamus of behavior‑lateralized mice after predatory exposure (8 mice in each group). a Influence of predator exposure on the expression of CRH mRNA in the hypothalamus. Chronic predator stress could significantly increase CRH expression. The normal control group (without considering behavioral lateralization) was used as the calibrator for normalization (*P < 0.05, **P < 0.01, ***P < 0.001). b The expression of CRH mRNA in the hypothalamus of behavior‑lateralized mice with predatory stress. Both in the left ‑pawed and right ‑pawed mice, CRH mRNA expression was greatly elevated after chronic stress, showing higher levels than those in the control and acute stress mice. The normal control group (without considering behavioral lateralization) was used as the calibrator for normalization (*P < 0.05, **P < 0.01, ***P < 0.001) Yang et al. Behav Brain Funct (2018) 14:12 Page 6 of 8 Fig. 4 The expression of GR in the hippocampus of behavior‑lateralized mice after predatory exposure (8 mice in each group). a Influence of predatory exposure on the expression of GR mRNA. The GR mRNA expression in the hippocampus was downregulated profoundly after acute stress and chronic stress. The normal control group (without considering behavioral lateralization) was used as the calibrator for normalization (*P < 0.05, **P < 0.01, ***P < 0.001). b, c The expression of GR mRNA in the hippocampus of behavior‑lateralized mice after predatory stress. Acute and chronic stress reduced the GR mRNA expression significantly, particularly in the left ‑pawed mice. For the normal control group, the GR mRNA in the left and right hippocampus of the left‑pawed mice was higher than that of the right ‑pawed mice. The normal control group (without considering behavioral lateralization) was used as the calibrator for normalization (*P < 0.05, **P < 0.01, ***P < 0.001). d–h The expression of the GR protein in the hippocampus of behavior‑lateralized mice after predatory exposure. The acute and chronic stress decreased the GR protein expression in the left and right hippocampus of both right‑pawed and left ‑pawed mice (relative density: *P < 0.05). Lc left‑pawed mice in control group, Las left‑pawed mice in acute stress group, Lcs left‑pawed mice in chronic stress group, Rc right ‑pawed mice in control group, Ras right ‑pawed mice in acute stress group, Rcs right‑pawed mice in chronic stress group Discussion might fuel long-lasting changes in brain stress. Generally, The activation of the stress system might lead to behav - the stressful response with the activation of the HPA axis ioral and immunoendocrine changes, which can improve is acute or at least of a limited duration. Our data sug- the ability to adjust to homeostasis [23, 24]. In the pre- gested that the integrated CS response was sensitized sent study, the acute and chronic cat-exposure model was by repeated predator exposure. When taking behavioral chosen to act as a psychological stressor to induce inter- lateralization into account, the right-pawed mice exhib- nal stress responses, and the impact on neural and hor- ited a higher elevation in the CS concentration after the monal indices was evaluated. Our results indicated that acute and chronic predator exposure than the left-pawed predator stress engaged an activation of the HPA axis that mice. The elevation of CS in the behavior-lateralized Yang et al. Behav Brain Funct (2018) 14:12 Page 7 of 8 mice may be related to the changes of the other elements in behavior asymmetric animals. Previous data demon- in the stress circuitry such as GR or CRH, which even- strated that the left-pawed mice have lower HPA-axis tually elicit the negative feedback regulation of the HPA reactivity; this alteration might be related to the consist- axis. The increased CS after stress had vital significance. ent alteration of CRH expression. Therefore, with lower It could regulate inflammation and use the body’s energy activity of the stress circuitry, the left-pawed mice may metabolism to deal with an emergent situation such display lower anti-inflammatory effects to stressful suf - as survival from predators. TNF-α is a multifunctional ferings than the right-pawed mice in the short-duration mediator, which can modulate the neuroimmunoendo- or long-time pathological conditions. These clues sup - crine system. Generally, a moderate plasma TNF-α level plied further evidence to prove the previous reports that can maintain the immune activation and inflammatory left-pawed mice might be more susceptible to immune reaction. The results showed that the plasma TNF-α disorders or certain brain disorders than right-pawed was significantly elevated after acute and chronic stress, mice, and to explain partially why left-paw preference and the chronic stress group showed a higher TNF-α or left-handedness is associated with a higher incidence level than the acute stress group. These findings implied of immune-mediated disorders [29–31]. In addition, GR that psychological stress might trigger immune activity is also a critical anti-inflammatory molecule in the cen - responsively. When we considered the effects of behavio - tral stress circuitry [14]. Studies demonstrated that GR ral asymmetry, TNF-α was increased in both left-pawed could suppress synthesis and release of some inflamma - and right-pawed mice after the predatory stress, and the tory chemical mediators and cytokines [14]. The present left-pawed mice tended to exhibit a high concentration of study showed that the GR expression in the hippocampus TNF-α. Such changes suggested that behavior lateraliza- of the control left-pawed mice was higher than that of tion may exert effects on the release of cytokines from the right-pawed control, while the GR expression in the immune cells to a certain extent, and the behavior-later- hippocampus of the left-pawed mice was downregulated alized mice may react to psychological stimulus hetero- profoundly after acute and chronic predator exposure. geneously. Previous studies have found that left-pawed The downregulation of the GR expression might lead to BALB/c mice exhibited a higher plasma IL-1β level and decrease of its function, especially its anti-inflammatory a higher activity of the HPA axis physiologically [15, 25]. capacity in left-pawed mice. Plasma IL-6 and ACTH were also involved in the regula- tion of behavioral lateralization with the challenge of LPS [16, 19, 21, 25]. Hence, overall, when confronting various Conclusion stressors including psychological stimuli or infection, dis- Taken together, the findings of our study indicated that tinct groups with hand/paw preference may adjust their predatory exposure can invoke heterogeneous varia- sensitivity of distinct stressful components coordinately, tion of the stressful elements of the neuroimmunoendo- so that they can facilitate internal homeostasis. crine central circuitry, which could promote complicated The hippocampal and hypothalamic regions have been responses and sensitization of the HPA axis in behavio- proven to exhibit high densities of adrenocorticosteroid- ral-lateralized animals. Due to these factors, the behav- binding sites within the brain, which exert pivot feedback ior-lateralized animals showed differential responses effects on the HPA axis [13, 16, 26]. Commonly, a stimu- to psychological stressors, which would be beneficial in lus can result in higher hormone secretion and activity of adapting to dynamic environments. the HPA axis, which are always involved in the negative feedback regulation of immune functions. According to Abbreviations our experimental design, the alteration of the HPA axis ACTH: adrenocorticotrophic hormone; CRH: corticotrophic hormone‑releasing could be determined in a naturalistic manner. In the cur- hormone; CS: corticosterone; ELISA: enzyme linked immunosorbent assay; GR: glucocorticoid receptor; HPA: hypothalamic–pituitary–adrenal axis; IL‑1β: rent study, the CRH mRNA expression in the hypothala- interleukin‑1β; IL ‑6: interleukin‑6; IFN‑Ɣ: interferon‑ gamma; PVN: paraventricu‑ mus elevated after acute and chronic stress, particularly lar nucleus; RPE: right paw entries; TNF‑α: tumor necrosis factor ‑α. after chronic stress. It appeared that such variation of Authors’ contributions the CRH mRNA in this region was necessary for induc- JCY and LZ contributed to performing all experiments and data analyses. ing facilitation of the HPA loop [11, 26–28]. Further- DJB contributed data analysis tools and technical support. JZ and XXC were more, both left-pawed and right-pawed mice exhibited involved in technical support and behavior tests. YS, KSL and ZFX contributed to creating the design of the study and the experimental paradigm, data elevation in the CRH expression after chronic preda- analyses and writing the manuscript; they should be regarded as the corre‑ tor exposure, and the left-pawed mice were inclined to sponding authors. All authors read and approved the final manuscript. exhibit a lower level than the right-pawed mice. These Author details phenomena may be ascribed to genetic differences in Department of Microbiology & Immunology, Shantou University Medical vulnerability to stress and the rate of steroid degradation College, 22 Xinling Road, Shantou 515041, Guangdong, People’s Republic Yang et al. Behav Brain Funct (2018) 14:12 Page 8 of 8 of China. First Affiliated Hospital of Shantou University Medical College, 10. de Andrade JS, Viana MB, Abrao RO, Bittencourt JC, Cespedes IC. 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Journal
Behavioral and Brain Functions – Springer Journals
Published: Dec 1, 2018
Keywords: neurosciences; neurology; behavioral therapy; psychiatry