Chronic restraint stress induced neurobehavioral alterations and histological changes in rat

Guedri, Kamilia; Frih, Hacène; Chettoum, Aziez; Rouabhi, Rachid

doi:10.1007/s13530-017-0312-6

Cited by 27 publications

(18 citation statements)

References 42 publications

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“…We show that anxiety-like behavior are present from week 1 and onward, using the Phenotyper tests developed by our group Prevot et al[44] The results obtained in the present study are consistent with previous findings reported using the Phenotyper test, and further confirm the validity of this test to detect anxiety-like behaviors in a repeatable fashion. Our results are also consistent with other findings showing that chronic restraint stress induces exacerbated anxiety-like behaviors in rodents [54, 55]. Guedri et al [55] previously showed that CRS in rats, 3hrs per day for 14 days induces anxiety-like behaviors observed in the open field and the elevated plus maze.…”

Section: Discussionsupporting

confidence: 93%

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Chatterjee

Knoch

et al. 2021

Preprint

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Depression is a leading cause of disabilities around the world, and the underlying mechanisms involved in its pathophysiology are broad and complex. Exposure to chronic stress is a risk factor for developing depressive-symptoms and contributes to cellular and molecular changes precipitating the emergence of symptoms. In the brain, excitatory neurons, inhibitory interneurons and supporting astroglial cells are all sensitive to chronic stress exposure and are known to be impaired in depression. Using an animal model of chronic stress, we assessed the impact of variable durations of chronic stress on the emergence of behavioral deficits and associated molecular changes in the prefrontal cortex (PFC), brain region highly sensitive to stress and impaired in depression. Mice were exposed to up to 35 days of chronic restraint stress and were assessed weekly on behavioral tests measuring anxiety and anhedonia. PFC Protein and RNA levels of specific markers of excitatory, inhibitory synapses and astroglia were quantified using western blot and qPCR, respectively. Correlation and integrative network analyses were used to investigated the impact of chronic stress on the different compartments. Results showed that chronic stress induces anxiety-like behaviors within 7 days, while anhedonia-like behaviors were observed only after 35 days. At the molecular level, alterations of many markers were observed, in particular with longer exposure to chronic stress. Finally, correlation analyses and integrative network analyses revealed that male and female mice react differently to chronic stress exposure and that some markers seem to be more correlated to behaviors deficits in males than in females. Our study demonstrate that chronic induces a dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, have different underlying pathologies.

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Section: Discussionsupporting

confidence: 93%

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Chatterjee

Knoch

et al. 2021

Preprint

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“…The aberration of the HPA axis may worsen brain damage, particularly in the PFC and HIP, due to the extent of expression of glucocorticoid receptors, contributing to the development of depressive symptoms (1,51). In this study, in agreement with previous reports, we found that RS exposure el-evated corticosterone concentration (38,52,53), which was markedly declined by E. amoenum treatment at doses of 150 and 300 mg/kg. Of interest, these results were accompanied by a noticeable attenuation of anxiety and depressivelike behaviors.…”

Section: Discussionsupporting

confidence: 91%

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Nouri

Farajdokht

Torbati

et al. 2019

Iran Red Crescent Med J

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Background: Echium amoenum (E. amoenum) is an Iranian medicinal plant with mood-enhancing effects. Objectives: This study was designed to investigate the effect of standardized E. amoenum hydroalcoholic extract on restraint stress (RS)-evoked anxiety-and-depressive-like behaviors in mice. Methods: This experimental study was conducted at the Tabriz University of Medical Sciences, Tabriz, Iran, in 2018. Doses of the hydroalcoholic extract of E. amoenum were optimized for rosmarinic acid (> %2 w/w) concentration of the extract. Other phytochemical indices, including total phenolic and flavonoid contents and radical scavenging activity, were also measured. For behavioral studies, 65 mice were randomly assigned into five groups (n = 13) of control, RS, RS + E75, RS + E150, and RS + E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups received E. amoenum extract (75, 150, and 300 mg/kg, p.o.) concomitantly with RS exposure. Anxiety-like behaviors were assessed by Elevated Plus Maze (EPM) and Open Field Test (OFT). Depression was assessed by the forced swim test (FST) and Tail Suspension Test (TST). Western blotting was performed to determine the protein levels of IL-1β, NF-κB, TNF-α, and IL-6 in the prefrontal cortex (PFC) and hippocampus (HIP). The concentrations of corticosterone, alanine aminotransferase, aspartate aminotransferase, and alanine phosphatase were also measured in serum. Results: Moderate and high doses of the extract ameliorated RS-induced anxiety-(P < 0.05 in OFT and EPM) and depressive-like (P < 0.05 and P < 0.01 in FST; P < 0.01 and P < 0.001 in TST) behaviors. These results were approved by decreased serum corticosterone levels (P < 0.05 and P < 0.001). Furthermore, E. amoenum reduced the protein expression of neuroinflammatory markers in the HIP and PFC subregions (significant at least at P < 0.05 for IL-1β, NF-κB, and TNF-α). Although RS slightly increased the serum levels of liver enzymes, no histopathological changes were seen in the liver of the RS or E. amoenum-treated groups. Conclusions: E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated inflammation and behavioral changes.

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“…Procedurally, learned helplessness was induced with random mild tail shocks, whereas, restraint stress (2hr/day) was applied consecutively for 14 days. Restraint rats have been shown to have anxiety and depression-like behaviors under varying amounts of time and restraint paradigms (Chiba et al, 2012; Guedri et al, 2017; Zhang et al, 2014); in our case we followed a similar restraint paradigm as mentioned by Guedri et al, (2017) who used a 3hr/day for 14-day paradigm.…”

Section: Discussionmentioning

confidence: 99%

Unfolded protein response and associated alterations in toll-like receptor expression and interaction in the hippocampus of restraint rats

Timberlake

Prall

Roy

et al. 2018

Psychoneuroendocrinology

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Recent evidence suggests that the cellular response to stress often elicits the unfolded protein response (UPR), which has an active role in major depression in emotionally relevant regions of the brain, such as the hippocampus. Much of the UPR activity has been found to be coalesced with the pro-inflammatory environment of the depressed brain. Specifically, downstream transcriptions of pro-inflammatory cytokines and increased regulation of candidate inflammatory mediators, such as toll-like receptors (TLRs), are promoted by the UPR. The present study examined the hippocampus associated expression profile of Tlr genes and their interaction with the UPR chaperone GRP94 in stress-induced rodent model of depression (restraint stress model). Also, the expression status of UPR related genes was evaluated in hippocampus using the same model. mRNA and protein levels of Tlr and UPR associated genes were examined by qRT-PCR and Western blot, respectively. Co-immunoprecipitation (Co-IP) method was used to determine the direct interaction between TLRs with GRP94 in depressed rat brain. The results showed that both UPR (Xbp-1, its spliced variant sXbp-1, Atf-6, Chop, and Grp94) and Tlr (2, 3, 4, 7 and 9) genes were significantly upregulated in the hippocampi of rats who were exposed to restraint stress. Similar upregulation was observed in the protein levels of the above-mentioned TLRs and the UPR chaperone protein GRP94 as well as total and phosphorylated forms of sensor proteins IRE1α and PERK. Further, a significantly increased interaction was observed between GRP94 and the activated TLR proteins. Since, increased inflammatory activity in vulnerable areas like hippocampus is coherently associated with depressed brain; our present data suggest that the UPR may be an integral part of increased activity of inflammatory regulations in depression.

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Chronic restraint stress induced neurobehavioral alterations and histological changes in rat

Cited by 27 publications

References 42 publications

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Unfolded protein response and associated alterations in toll-like receptor expression and interaction in the hippocampus of restraint rats

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