Chronic Restraint Stress Model Research Articles

Fucoidan exerts antidepressant-like effects in mice via regulating the stability of surface AMPARs

The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown seaweeds with anti-inflammatory activity. However, the antidepressant effects of fucoidan on chronic stress-induced depressive-like behaviors have not been well elucidated. Here, we used two different depressive-like mouse models, lipopolysaccharide (LPS) and chronic restraint stress (CRS) models, to explore the detailed molecular mechanism underlying its antidepressant-like effects in C57BL/6J mice by combining multiple behavioral, molecular and immunofluorescence experiments. Adenovirus-mediated overexpression of caspase-1 and pharmacological inhibitors were also used to clarify the antidepressant mechanisms of fucoidan. We found that acute administration of fucoidan did not produce antidepressant effects in the tail suspension test (TST) and forced swim test (FST). Interestingly, chronic fucoidan administration not only dose-dependently reduced stress-induced depressive-like behaviors in the TST, FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT), but also alleviated the downregulation of brain-derived neurotrophic factor (BDNF)-dependent synaptic plasticity via inhibiting caspase-1-mediated inflammation in the hippocampus of mice. Moreover, fucoidan significantly ameliorated behavioral and synaptic plasticity abnormalities in the overexpression of caspase-1 in the hippocampus of mice. Furthermore, blocking BDNF abolished the antidepressant-like effects of fucoidan in mice. Therefore, our findings clearly indicate that fucoidan provides a potential supplementary noninvasive treatment for depression by inhibition of hippocampal inflammation.

363 CRH is a stimulator for both connective tissue- and mucosal-type mast cells

It is well-known that psychological stress exacerbates various types of diseases including atopic dermatitis and allergic rhinitis. One of crucial cells in immune responses, mast cell (MC)s, are activated in those diseases and play central roles in their pathogenesis. Hypothalamic-pituitary-adrenal (HPA) axis is an essential endocrine system of reaction to stress. However, the existence of local HPA axis is also reported within the human skin. Among the HPA axis-related hormone, corticotropin-releasing hormone (CRH) is regarded as a potent central stress mediator. We have previously shown that the locally secreted CRH activates connective tissue type MCs (CT-MC)s degranulation and differentiation by organ cultured human hair follicles (HF)s. Here, we focused on the effect of CRH on mucosal-type (M-)MCs biology compared to CT-MCs. Using the previously established human nasal polyp organ culture, CRH was detected both in gene and protein levels. CRH significantly enhanced the expression of both melanocortin 2 receptor and glucocorticoid receptor, while hydrocortisone decreased CRH receptor expression, suggesting the presence of positive and negative feedback system as seen in human HFs. Similar with CT-MCs, CRH significantly increased M-MCs number and stimulated degranulation. In contrast to CT-MCs, CRH enhanced M-MCs proliferation. Just seen in human HFs, CRH increased the expression of stem cell factor (SCF), a growth factor for MCs, suggesting that SCF is also involved in CRH-induced M-MCs activation. Finally, we checked M-MCs in nasal mucosa of chronic restraint stress model mouse. As a result, the number of degranulated MCs significantly increased in nasal mucosa. Current results suggest that the local HPA axis exists not only in human skin but also in nasal mucosa. Since CRH is a stimulator for both CT-MCs and M-MCs, controlling of HPA axis-related hormones may be a key target for establishing novel therapy for atopic dermatitis and allergic rhinitis.

Changes in gonadal function at different stages of chronic restraint stress-induced depression animals

The aim of this study was to determine the time-dependent changes in adolescent male gonadal function due to chronic restraint stress (CRS)-induced depression in a rat model and to elucidate the underlying mechanism. CRS was established in adolescence male Wistar rats by placing the animals in a cylinder for 3 h every day for 28 days, during which time the general behavior and serum hormonal levels were routinely monitored. The CRS model rats showed anxiety-like behavior in the open field test (OFT) and sucrose consumption test, and their body weights also decreased significantly on the 14th, 21st and 28th days. The CRS rats showed a significant decrease in serum 5-hydroxytryptamine (5-HT) after 14 days of restraint and an increase in the CORT and NE levels after 21 days of restraint, while the serum GnRH levels increased significantly on the 14th and 21st days and decreased significantly over the last 7 days. In contrast, the FSH and LH levels decreased significantly from the 14th day to the 28th day, while the PRL and E2 levels were significantly higher during the same time period compared to those of the controls. The serum T levels also decreased significantly in the CRS group on the 21st and the 28th days, with the lowest levels occurring on day 28. Histopathological examination showed that testicular damage was aggravated during CRS. In addition, the levels of MDA, CytC and 8-OHDG increased significantly, while those of SOD decreased significantly in the CRS rats testicular mitochondrial. These results indicate that the gonadal function is altered at different stages of CRS, which can be attributed to changes in neurotransmitters and PRL that affect GnRH levels in the hypothalamus and subsequently regulate the serum T levels. In addition, excessive production of CORT impairs the testicle in adolescent period via enhanced oxidative damage, which eventually leads to gonadal dysfunction.

The antidepressant effects of apigenin are associated with thepromotion of autophagy via the mTOR/AMPK/ULK1 pathway.

The present study aimed to investigate whether apigenin elicits antidepressant effects in depressant‑like mice via the regulation of autophagy. The depressant‑like behaviors were established in a chronic restraint stress model. Male BALB/c mice were subjected to restraint stress for 6h/day for a period of 21days, and deficits in sucrose preference, tail suspension and forced swim tests were confirmed to be improved following oral apigenin. To investigate the underlining mechanisms, the hippocampal levels of p62 and microtubule‑associated protein light chain 3‑II/I (LC3‑II/I) were measured using western blot analysis. The expression levels of LC3‑II/I and p62 indicated that the significantly inhibited autophagy level induced by chronic restraint stress can be increased following apigenin treatment. Similar to the level of autophagy, the expression levels of adenosine monophosphate‑activated protein kinase (AMPK) and Unc‑51 like autophagy activating kinase‑1 were downregulated after chronic restraint stress stimulation and, subsequently upregulated following treatment with apigenin. Conversely, the levels of mammalian target of rapamycin (mTOR) were increased in chronic restraint stress mice and inhibited by apigenin. Collectively, the present findings indicated that apigenin potentially promotes autophagy via the AMPK/mTOR pathway and induces antidepressive effects in chronic restraint stress mice.

The positive allosteric modulator at mGlu2 receptors, LY487379, reverses the effects of chronic stress-induced behavioral maladaptation and synaptic dysfunction in the adulthood.

Chronic stress induces maladaptive neural responses in several brain areas including hippocampus. It has been demonstrated that chronic stress exposure induced a downregulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors, which would reduce the negative feedback role exerted by these receptors. The reduced availability of these receptors would enhance glutamate overflow in the hippocampus, supporting the hypothesis that hippocampal glutamatergic neurotransmission plays a key etiopathological determinant in stress-induced neuropsychiatric disorders. Since modulation of glutamatergic neurotransmission has been shown to represent an interesting pharmacological tool to treat psychiatric disorders, in the present study we have investigated the effects of the mGlu2 receptor positive allosteric modulator (PAM) LY487379. The rational bases of our study were: (a) chronic restraint stress (CRS) application in C57/BALB6 mouse induced a loss of resilience at the behavioral, biochemical, and electrophysiological level; (b) a superimposed familiar stressor (restraint) but not unfamiliar (i.e., forced swim stress) completely reversed the effects of CRS. Using the CRS model, in the present study we have investigated the effects of LY487379, an mGlu2 PAM, as well as a superimposed familiar stressor (acute restraint stress-ARS), on the immobility time at the tail suspension test and electrophysiological profile of glutamatergic transmission in the dentate gyrus (DG).

Alterations in the BDNF–mTOR Signaling Pathway in the Spinal Cord Contribute to Hyperalgesia in a Rodent Model of Chronic Restraint Stress

Stress is a non-specific, systemic, physiological response of the body to strong internal and external environmental stimuli. Accumulating evidence has suggested that stress, particularly chronic restraint stress (CRS), can reduce pain threshold and increase pain sensitivity. However, pathogenic and therapeutic mechanisms underlying CRS remain unclear. Here, we aimed to investigate roles of the brain-derived neurotrophic factor (BDNF)–mammalian target of rapamycin (mTOR) signaling pathway in CRS-induced abnormal pain sensitivity. CRS was successfully mimicked 7 days after model development, and paw withdrawal mechanical threshold (PWMT) and tail-flick latency (TFL) were evaluated. CRS significantly altered BDNF and mTOR phosphorylation in the anterior cingulate cortex and spinal cord but not in the hippocampus. On day 7, a single dose of 7,8-dihydroxyflavone, an activator of BDNF–tropomyosin receptor kinase B, was administered via intraperitoneal or intrathecal injection. Notably, only the intrathecal injection improved PWMT and TFL. Additionally, an intraperitoneal injection of rapamycin, an mTOR inhibitor, failed to induce any behavioral changes, whereas a single intrathecal injection of rapamycin improved abnormal CRS-induced PWMT and TFL. In conclusion, CRS can induce abnormal pain sensitivity, probably by altering the BDNF–mTOR signaling pathway in the spinal cord.

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser.

The effectiveness of transcranial photobiomodulation (TPBM) in treating anxiety and depression disorders is a demonstrated and identified issue. However, the optimum therapeutic dose and the underlying mechanism of action are not fully understood. In this study, the therapeutic effects of three different near-infrared (NIR) doses on anxiety- and depression-like behaviors as well as cerebral levels of serotonin (5-HT) and nitric oxide (NO) were evaluated in a mouse model of chronic restraint stress (CRS). CRS procedure (3 hours/day, over 3 weeks) was performed as a typical stress model to study anxiety and depression along with laser treatment (3 times/week, over 3 weeks), which began simultaneously with CRS. A NIR diode laser (810 nm wavelength, 10 Hz) with the output power of 200 mW and power density of 4.75 W/cm2 was implemented to deliver three different doses of 4, 8, and 16 J/cm2 to the cerebral cortex of mice. Behavioral experiments including open field, tail suspension, and elevated plus maze tests as well as serum cortisol levels were assessed to evaluate the anti-anxiety and anti-depressive effects of NIR TPBM. The changes of 5-HT and NO levels in the prefrontal cortex (PFC) and hippocampus (Hipp) were assessed. CRS procedure induced anxiety- and depression-like behaviors, increased serum cortisol levels, decreased 5-HT and increased NO levels in the PFC and Hipp areas. NIR TPBM improved behavioral results, decreased serum cortisol levels, increased 5-HT and decreased NO concentrations in the PFC and Hipp. A dose of 8 J/cm2 of NIR TPBM showed the maximum effects on behavioral and molecular results, while a decline was observed from the optimum effects at both lower (4 J/cm2 ) and higher (16 J/cm2 ) doses. Our results demonstrated that NIR TPBM had an anti-anxiety and anti-depressive effect in CRS mice, which is probably linked to increasing 5-HT and decreasing NO levels in the PFC and Hipp areas. Also, the maximum anti-anxiety and anti-depressive effect was produced at dose of 8 J/cm2 . Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Abstract # 3181 Effect of acute and chronic stress on the expression of GPR43 and GPR41 receptors in murine ileum and colon epithelial cells

GPR41 and GPR43 receptors are located at the level of the ileum and colon in the enteroendocrine cells, being activated by short-chain bacterial fatty acids, products of fermentation, these become a key to activate the mechanisms involved in this intestinal homeostasis. GPR43 and GPR41 mediate inflammatory processes such as colitis, but it has not been demonstrated their participation in vivo models of stress. In a model of acute and chronic restraint stress BALB/c mice we evaluated their expression. The measurement of serum corticosterone was performed to validate our model. Gene expression of Gpr41/Gpr43 through qPCR and protein expression of GPR41/GPR43 by Western Blot in both Large Intestine (IG) and Small Intestine (ID). Our results show that stress increases corticosterone levels being higher in chronic stress. Gene expression may show an increase for both receptors in chronic stress. Protein expression, unlike gene, has a greater increase in acute stress, except for GPR41 in ID where its increase is not significant. This suggests that an acute stimulation increases the expression of this receptor to conserve intestinal homeostasis, which initially deplete the gene machinery and then increase it by the constant appearance of the stressor stimulus although there seem to be post-translational mechanisms that do not allow. This shows us that the gradual increase of corticosterone apparently affects the expression of the protein of both receptors.

Effect of co-administration of zinc and fluoxetine in the chronic restraint stress model of depression in mice

effect of co-administration of zinc and fluoxetine in the chronic restraint stress model of depression in mice

Hyperglycemia Induced by Chronic Restraint Stress in Mice Is Associated With Nucleus Tractus Solitarius Injury and Not Just the Direct Effect of Glucocorticoids.

Chronic restraint stress (CRS) can affect hypothalamic-pituitary-adrenal (HPA) axis activity and increase glucocorticoid levels. Glucocorticoids are stress hormones that regulate multiple aspects of energy homeostasis. Stress also impairs glucose tolerance. The aim of this study was to investigate the cause of insulin-resistant hyperglycemia during CRS. We produced the CRS models (a 7-day restraint followed by a 3-day free moving procedure, total of 4 cycles for 40 days) in mice, detected the parameters related to glucose metabolism, and compared them to those of the dexamethasone (DEX) injection (0.2 mg/kg i.p., also a 4 cycle procedure as the CRS). The results showed that the CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulin-resistant hyperglycemia in about 1/3 of the individuals, and all the restrained mice had adrenal hypertrophy. CRS induced the apoptosis of neurons in the anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) in the hyperglycemic mice, and acNTS mechanical damage also led to insulin-resistant hyperglycemia. In contrast, in the DEX-treated mice, adrenal gland atrophy was evident. The glucose and insulin tolerance varied with the delay of determination. DEX exposure in vivo does not induce the apoptosis of neurons in NTS. This study indicates that restraint stress and DEX induce metabolic disorders through different mechanisms. During CRS, injury (apoptosis) of glucose-sensitive acNTS neurons cause dysregulation of blood glucose. This study also suggests the mouse restraint stress model has value as a potential application in the study of stress-induced hyperglycemia.

Stress-induced changes in social dominance are scaled by AMPA-type glutamate receptor phosphorylation in the medial prefrontal cortex

The establishment and maintenance of social dominance are critical for social stability and the survival and health of individual animals. Stress lead to depression and a decrease in the social status of depressed persons is a risk factor for suicide. Therefore, we explored the mechanistic and behavioral links among stress, depression, and social dominance and found that mice subjected to chronic restraint stress (CRS), an animal model of stress-induced depression, showed decreased social dominance as measured by a dominance tube test. Importantly, this submissive behavior was occluded by the antidepressant, fluoxetine, a selective serotonin reuptake inhibitor. It is known that social dominance is controlled by synaptic efficacy in the medial prefrontal cortex (mPFC) and that AMPA-type glutamate receptor (AMPA-R) is a key molecule for synaptic efficacy. We found that the phosphorylation on AMPA-R was bidirectionally changed by CRS and fluoxetine in the mPFC of mice with CRS. Moreover, we found a strong correlation between social dominance and AMPA-R phosphorylation that regulates synaptic efficacy by modulating the synaptic targeting of AMPA-R. Our correlational analysis of the behavior and biochemistry of the CRS model suggests that AMPA-R phosphorylation in the mPFC may serve as a biomarker of social dominance related to stress.

The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice.

Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.

Vaccinium bracteatum Leaf Extract Reverses Chronic Restraint Stress-Induced Depression-Like Behavior in Mice: Regulation of Hypothalamic-Pituitary-Adrenal Axis, Serotonin Turnover Systems, and ERK/Akt Phosphorylation.

The leaves of Vaccinium bracteatum Thunb. are a source of traditional herbal medicines found in East Asia. The present study aimed to evaluate the mechanisms underlying the antidepressant-like effects of water extract of V. bracteatum Thunb. leaves (VBLW) in a mouse model of chronic restraint stress (CRS) and to identify the possible molecular in vitro mechanisms of the neuroprotective effects. The CRS-exposed mice were orally administered VBLW (100 and 200 mg/kg) daily for 21 days consecutively. The behavioral effects of VBLW were assessed through the forced swim test (FST) and the open field test (OFT). The levels of serum corticosterone (CORT), corticotropin releasing hormone (CRH), and adrenocorticotropin hormone (ACTH), brain monoamines, such as serotonin, dopamine, and norepinephrine, and serotonin turnover by tryptophan hydroxylase 2 (TPH2), serotonin reuptake (SERT), and monoamine oxidase A (MAO-A) were evaluated, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway. CRS-exposed mice treated with VBLW (100 and 200 mg/kg) showed significantly reduced immobility time and increased swimming and climbing times in the FST, and increased locomotor activity in the OFT. Moreover, CRS mice treated with VBLW exhibited significantly decreased CORT and ACTH, but enhanced brain monoamine neurotransmitters. In addition, CRS mice treated with VBLW had dramatically decreased protein levels of MAO-A and SERT, but increased TPH2 protein levels in the hippocampus and the PFC. Similarly, VBLW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and the PFC. Furthermore, VBLW showed neuroprotective effects via increased CREB phosphorylation in CORT-induced cell injury that were mediated through the ERK/Akt/mTOR signaling pathways. These results suggested that the antidepressant-like effects of VBLW might be mediated by the regulation of the HPA axis, glucocorticoids, and serotonin turnover, such as TPH2, SERT, and MAO-A, as well as the concentration of monoamine neurotransmitters, and the activities of ERK and Akt phosphorylation, which were possibly associated with neuroprotective effects.

Hippocampal metabolic differences implicate distinctions between physical and psychological stress in four rat models of depression

Major depressive disorder (MDD) is a heterogeneous and multi-factorial disorder, and the underlying molecular mechanisms remain largely unknown. However, many studies have indicated that the molecular mechanisms underlying depression in response to different stress may differ. After screening, 28–30 rats were included in each model of depression (chronic unpredictable mild stress (CUMS); learned helplessness (LH); chronic restraint stress (CRS); or social defeat (SD)). Non-targeted gas chromatography-mass spectrometry was used to profile the metabolic changes in the hippocampus. As a result, all four models exhibited significant depression-like behavior. A total of 30, 24, 19, and 25 differential metabolites were identified in the CUMS, LH, CRS, and SD models, respectively. Interestingly, the hierarchical clustering results revealed two patterns of metabolic changes that are characteristic of the response to cluster 1 (CUMS, LH) and cluster 2 (CRS, SD) stress, which represent physical and psychological stress, respectively. Bioinformatic analysis suggested that physical stress was mainly associated with lipid metabolism and glutamate metabolism, whereas psychological stress was related to cell signaling, cellular proliferation, and neurodevelopment, suggesting the molecular changes induced by physical and psychological stress were different. Nine shared metabolites were opposite in the directions of change between physical and psychological models, and these metabolites were associated with cellular proliferation and neurodevelopment functions, indicating the response to physical and psychological stress was different in the activation and deactivation of the final common pathway to depression. Our results provide a further understanding of the heterogeneity in the molecular mechanisms of MDD that could facilitate the development of personalized medicine for this disorder.

Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations.

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

Antidepressant Effects of Vaccinium bracteatum via Protection Against Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis.

The present study evaluates the anti-oxidative stress activity of Vaccinium bracteatum Thunb. fruit extract (VBFW) to identify the mechanisms responsible for its antidepressant-like effects. To evaluate the antidepressant and anti-oxidant effects of VBFW, malondialdehyde (MDA), serotonin transporter (SERT), and monoamine oxidase A (MAO-A) levels were measured in a mouse model of chronic restraint stress (CRS). The underlying mechanisms preventing oxidative stress and neuronal apoptosis were investigated using in vitro models of hydrogen peroxide (H2O[Formula: see text]-induced neuronal damage. The results showed that VBFW treatment (200[Formula: see text]mg/kg) significantly reduced MDA, SERT, and MAO-A levels in the prefrontal cortex of CRS mice. Furthermore, VBFW (30[Formula: see text][Formula: see text]g/mL) exhibited protective effects against H2O2-induced cell death via inhibition of the H2O2-induced increase in Bax and decrease in Bcl-2 levels within the mitochondria of SH-SY5Y cells. Furthermore, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) exerted protective effects against H2O2-induced cell death through inhibition of key mitochondria-associated apoptotic proteins such as cytochrome c, caspase-3 and PARP. Additionally, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) could improve the activity of anti-oxidant enzymes (such as SOD and catalase) in H2O2-treated SH-SY5Y cells. These results suggest that the antidepressant and anti-oxidant effects of VBFW might be mediated by the regulation of SERT and MAO-A, and possibly associated with regulation of oxidative stress-induced apoptosis.

Effects of two chronic stresses on mental state and hair follicle melanogenesis in mice.

Growing bodies of data show that psychological stress can be associated with hair loss and vitiligo. Researchers have revealed that stress could indeed inhibit hair growth in vivo, but the relationship between chronic stress and melanogenesis remains unknown. In this study, we established two types of stress models, chronic restraint stress (CRS) and chronic unpredicted mild stress (CUMS) mice models, and explored the possible role of stress in mice hair follicle melanogenesis. We found that stress changed hippocampal morphology, decreased 5-HT level in brain and skin and down-regulated 5-HT1A receptor expression in hippocampal CA1 region and skin. The alterations of 5-HT and 5-HT1A receptor might be a threshold of central stress to associate with the behaviour changes. Both two stresses caused cellular damage of melanocytes and inhibition of keratinocytes proliferation in HF, which made the synthetic pigment loss. CRS which was considered primarily as a "psychological" stressor had the lower melanin production in HF, as well as the level of 5-HT in skin was down-regulated more than those in CUMS group.

Lack of interleukin-13 receptor \u03b11 delays the loss of dopaminergic neurons during chronic stress

BackgroundThe majority of Parkinson’s disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress. Here, we tested the hypothesis that the interleukin-13 receptor alpha 1 (IL-13Rα1), a cytokine receptor whose activation increases the vulnerability of dopaminergic neurons to oxidative damage, participates in the stress-dependent damage of these neurons.MethodsMice were subject to daily sessions of 8 h (acute) stress for 16 weeks (5 days a week), a procedure previously showed to induce loss of dopaminergic neurons in the SNc. The source and the kinetics of interleukin-13 (IL-13), the endogenous ligand of IL-13Rα1, were evaluated 0, 1, 3, 6, and 8 h and at 16 weeks of stress. Identification of IL-13 producing cell-type was performed by immunofluorescent and by in situ hybridization experiments. Markers of oxidative stress, microglia activation, and the number of dopaminergic neurons in IL-13Rα1 knock-out animals (Il13ra1Y/−) and their wild-type littermates (Il13ra1Y/+) were evaluated at 16 weeks of stress and at 20 weeks, following a 4 week non-stressed period and compared to non-stressed mice.ResultsIL-13 was expressed in microglial cells within the SN and in a fraction of the tyrosine hydroxylase-positive neurons in the SNc. IL-13 levels were elevated during daily stress and peaked at 6 h. 16 weeks of chronic restraint stress significantly reduced the number of SNc dopaminergic neurons in Il13ra1Y/+mice. Neuronal loss at 16 weeks was significantly lower in Il13ra1Y/− mice. However, the loss of dopaminergic neurons measured at 20 weeks, after 4 weeks of non-stress following the 16 weeks of stress, was similar in Il13ra1Y/+ and Il13ra1Y/− mice.ConclusionsIL-13, a cytokine previously demonstrated to increase the susceptibility of SNc dopaminergic neurons to oxidative stress, is elevated in the SN by restraint stress. Lack of IL-13Rα1 did not prevent nor halted but delayed neuronal loss in the mouse model of chronic restraint stress. IL-13/IL-13Rα1 may represent a target to reduce the rate of DA neuronal loss that can occur during severe chronic restraint stress.

Pharmacological and biochemical modulation of stress markers by L-NAME and L-Ascorbic acid in chronic restraint model in Wistar rats

Background: Stress is the psycho-physiologic reaction of the body to diverse stimuli including emotional or physical stimuli that imbalance the homeostasis and is also known to trigger various stress markers. Despite the stressors of different types, chronic stress in particular, is known to influence the physiological milieu and breakdown of adaptive mechanisms consequently aggravating the morbid states. Aims and Objectives: The present study was designed to evaluate the modulatory role of stress marker by N-nitro-L-arginine-methyl ester (L-NAME) and L-Ascorbic acid (L-AA) in experimental model of chronic restraint stress (RSx21) in Wistar rats.Materials and Methods: MDA and GSH levels were determined by the method of Okhawa et al 1979 and Ellman 1959 respectively, the SOD and catalase levels were estimated by the method of Nandi and Chatterjee 1988 and Aebi 1984 respectively.Results: Results from our study reveal the significant enhancement of malondialdehyde (MDA) level while significant attenuation of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase levels in chronic stress group compared with vehicle (non-stress) group. The MDA level was found to be increased by L-NAME (10 and 50 mg/kg) in chronic restraint (RSx21) induced rats as compared to vehicle treated RS group. Antioxidant L-AA (100 and 200 mg/kg) significantly reduced MDA level in chronic stress situation. However, L-NAME and L-Ascorbic Acid were found to cause an increase in level of plasma SOD, GSH and catalase when compared with vehicle treated RS group. On the other hand, L-AA (100 and 200 mg/kg) reversed these RS induced changes in these oxidative parameters.Conclusions: Hence, results from the study underlined the intricate role of antioxidants as evidenced by reversal of oxidative stress markers that command a vital role in the development of morbid condition.Asian Journal of Medical Sciences Vol.8(1) 2017 15-20

Evaluation of 5-HT1A and 5-HT2A receptors in a rat model of chronic restraint stress: antidepressant-like effects of albiflorin

Evaluation of 5-HT1A and 5-HT2A receptors in a rat model of chronic restraint stress: antidepressant-like effects of albiflorin