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What is Chronic immobilization stress (CIS)?

What is Chronic immobilization stress (CIS)?


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I am trying to self study BNDF a little bit when I found this article:

Abstract Stress impacts multiple systems within the CNS, including the hippocampus. A key molecular mediator in hippocampal functions, including learning and memory, is brain-derived neurotrophic factor (BDNF). BDNF mRNA is reported to be decreased following chronic (every day) immobilization stress (CIS) in the rat, however the effect on protein is unknown. Utilizing a mouse model of CIS, the hypothesis that total hippocampal BDNF protein, in addition to BDNF mRNA, would be decreased was tested. The effects of intermittent (alternating day) immobilization and cold stress on hippocampal BDNF protein levels was also examined.

In this study it was demonstrated that CIS results in a small (8 per cent decrease relative to non-stressed controls), but significant (p = 0.0013) decrease in the exon coding for mature BDNF (exon VI). In addition, there was a significant (34 per cent, p = 0.005) decrease in the mRNA coding for exon I in the stressed animals. Contrary to expectations, however, CIS resulted in a significant (116 per cent, p = 0.0087) increase in hippocampal BDNF protein levels. Furthermore, both intermittent immobilization and chronic cold stress both increased BDNF protein levels. Chronic stress, therefore, differentially regulates BDNF mRNA and protein levels in the hippocampus. Copyright © 2004 John Wiley & Sons, Ltd.

I'm really curious what they mean with CIS: Chronic immobilization stress. I can't find anything on the internet that actually explains what this is.


There are >1200 articles tagged "chronic immobilization stress" on pubmed.

From Hennebelle et al. (2012):

Half of the 6-month old male rats from each dietary group were subjected to a validated chronic stress procedure (Buyntsky and Mostosky, 2009) based on a restraint stress procedure adapted from Veena et al, [32]. Rats were placed in wire mesh restrainers for 6 h a day (fom 10 am to 16 pm) for 21 days (5 days a week) over a period of 4 weeks. Unstressed rats were handled weekly. The unstressed and stressed animals were housed in different rooms.

Hennebelle, H., et al. 2012. Influence of Omega-3 Fatty Acid Status on the Way Rats Adapt to Chronic Restraint Stress. PLoSOne 7: e42142.


A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, therapeutic treatments for depression or research on depression is scarce. Thus, in the present paper, we propose a mouse model of depression induced by movement restriction. Chronic mild stress (CMS) is a well-known technique to induce depressive-like behavior. However, it necessitates a complex procedure consisting of a combination of various mild stresses. In contrast, chronic immobilization stress (CIS) is a readily accessible chronic stress model, modified from a restraint model that induces depressive behavior by restricting movement using a restrainer for a certain period. To evaluate the depressive-like behaviors, the sucrose preference test (SPT), the tail suspension test (TST), and the ELISA assay to measure stress marker corticosterone levels are combined in the present experiment. The described protocols illustrate the induction of CIS and evaluation of the changes in behavior and physiological factors for the validation of depression.


Stress enhances hippocampal neuronal synchrony and alters ripple-spike interaction

Adverse effects of chronic stress include anxiety, depression, and memory deficits. Some of these stress-induced behavioural deficits are mediated by impaired hippocampal function. Much of our current understanding about how stress affects the hippocampus has been derived from post-mortem analyses of brain slices at fixed time points. Consequently, neural signatures of an ongoing stressful experiences in the intact brain of awake animals and their links to later hippocampal dysfunction remain poorly understood. Further, no information is available on the impact of stress on sharp-wave ripples (SPW-Rs), high frequency oscillation transients crucial for memory consolidation. Here, we used in vivo tetrode recordings to analyze the dynamic impact of 10 days of immobilization stress on neural activity in area CA1 of mice. While there was a net decrease in pyramidal cell activity in stressed animals, a greater fraction of CA1 spikes occurred specifically during sharp-wave ripples, resulting in an increase in neuronal synchrony. After repeated stress some of these alterations were visible during rest even in the absence of stress. These findings offer new insights into stress-induced changes in ripple-spike interactions and mechanisms through which chronic stress may interfere with subsequent information processing.


Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1-Oxytocin-Proopiomelanocortin Neural Pathway in the Hypothalamus

Background: Chronic stress is an important risk factor for depression. The nesfatin-1 (NES1)-oxytocin (OT)-proopiomelanocortin (POMC) neural pathway, which is involved in the stress response, was recently shown to have an anorectic effect in the hypothalamus. Our previous study showed that Xiaoyaosan, a well-known antidepressant used in traditional Chinese medicine, effectively relieved appetite loss induced by chronic immobilization stress (CIS). However, whether Xiaoyaosan ameliorates depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway remains unclear. Objective: To investigate whether the antidepressant-like and anti-anorexia effects of Xiaoyaosan are related to the NES1-OT-POMC neural pathway in the hypothalamus. Methods: Rats were randomly divided into control, CIS, Xiaoyaosan treatment, and fluoxetine treatment groups. The rats in the CIS, Xiaoyaosan treatment, and fluoxetine treatment groups were subjected to CIS for 21 consecutive days, during which they were administered distilled water, a Xiaoyaosan decoction [3.854 g/(kg·d)] or fluoxetine [1.76 mg/(kg·d)], respectively, by gavage, and their body weights and food intake were monitored daily. The rats were subsequently subjected to the open field test and sucrose preference test. Then, the expression levels of corticosterone and NES1 in the serum and the expression levels of NES1, OT, POMC, and melanocortin-4 receptor (MC4R) in the hypothalamus were determined by real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunochemistry. Furthermore, immunofluorescence double staining was used to determine whether related proteins in the hypothalamic NES1-OT-POMC neural pathway were co-expressed. Results: Compared to control rats, rats exposed to CIS exhibited gradually less food intake and lower body weights and significantly increased concentrations of NES1 in the serum and paraventricular nucleus. Moreover, the expression levels of POMC, OT, and MC4R in the hypothalamus were significantly higher in the CIS group than those in the control group. However, these changes were reversed by pretreatment with Xiaoyaosan and fluoxetine. Specifically, the expression levels of members of the NES1-OT-POMC neural pathway were lower in the Xiaoyaosan-treated group than in the CIS group. Conclusion: Xiaoyaosan ameliorates CIS-induced depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway in the hypothalamus.

Keywords: Xiaoyaosan anorexia chronic immobilization stress depression nesfatin-1.

Copyright © 2019 Ma, Li, Yan, Jiao, Wang, Hou, Jiang, Liu and Chen.

Figures

Study schedule. Before the experiment,…

Study schedule. Before the experiment, the animals were allowed a 7-day adaptation period.…

Xiaoyaosan ameliorates CIS-induced depression-like behaviors.…

Xiaoyaosan ameliorates CIS-induced depression-like behaviors. (A) The paths taken by rats in each…

Xiaoyaosan ameliorates CIS-induced anorexia. (A)…

Xiaoyaosan ameliorates CIS-induced anorexia. (A) Changes in food intake. (B) Changes in body…

Effects of Xiaoyaosan on serum…

Effects of Xiaoyaosan on serum CORT and NES1 levels in rats after CIS.…

Effects of Xiaoyaosan on the…

Effects of Xiaoyaosan on the NES1-OT-POMC neural pathway in the hypothalamus. mRNA expression…

Effect of Xiaoyaosan on NES1…

Effect of Xiaoyaosan on NES1 immunolabeling in the hypothalamus. (A) Representative micrographs showing…

Effects of Xiaoyaosan on POMC…

Effects of Xiaoyaosan on POMC and OT immunolabeling in the hypothalamus. (A) Representative…

Co-expression of NES1 and POMC…

Co-expression of NES1 and POMC or OT in the rat hypothalamus. Hypothalamic sections…

Potential mechanism by which Xiaoyaosan…

Potential mechanism by which Xiaoyaosan exerts antidepressant-like and anti-anorexia effects.


Glutamine Supplementation Prevents Chronic Stress-Induced Mild Cognitive Impairment

We recently reported that glutamine (Gln) supplementation protected glutamatergic neurotransmission from the harmful effects of chronic stress. Altered glutamatergic neurotransmission is one of the main causes of cognitive disorders. However, the cognitive enhancer function of Gln has not been clearly demonstrated thus far. Here, we evaluated whether and how Gln supplementation actually affects chronic stress-induced cognitive impairment. Using a chronic immobilization stress (CIS) mouse model, we confirmed that chronic stress induced mild cognitive impairment (MCI) and neuronal damage in the hippocampus. In contrast, Gln-supplemented mice did not show evidence of MCI. To investigate possible underlying mechanisms, we confirmed that CIS increased plasma corticosterone levels as well as brain and plasma levels of reactive oxygen/nitrogen species. CIS also increased levels of inducible nitric oxide synthase and NADPH oxidase subunits (p47 phox and p67 phox ) in both the prefrontal cortex and CA1 region of the hippocampus. CIS decreased the number of synaptic puncta in the prefrontal cortex and hippocampus, but these effects were inhibited by Gln supplementation. Taken together, the present results suggest that Gln is an effective agent against chronic stress-induced MCI.

Keywords: Chronic stress glutamine mild cognitive impairment oxidative stress.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript, or in the decision to publish the results.


Sex differences after chronic stress in the expression of opioid-, stress- and neuroplasticity-related genes in the rat hippocampus

Opioid peptides and their receptors re-organize within hippocampal neurons of female, but not male, rats following chronic immobilization stress (CIS) in a manner that promotes drug-related learning. This study was conducted to determine if there are also sex differences in gene expression in the hippocampus following CIS. Adult female and male rats were subjected to CIS (30 min/day) for 10 days. Twenty-four hours after the last stressor, the rats were euthanized, the brains were harvested and the medial (dentate gyrus/CA1) and lateral (CA2/CA3) dorsal hippocampus were isolated. Following total RNA isolation, cDNA was prepared for gene expression analysis using a RT 2 Profiler PCR expression array. This custom designed qPCR expression array contained genes for opioid peptides and receptors, as well as genes involved in stress-responses and candidate genes involved in synaptic plasticity, including those upregulated following oxycodone self-administration in mice. Few sex differences are seen in hippocampal gene expression in control (unstressed) rats. In response to CIS, gene expression in the hippocampus was altered in males but not females. In males, opioid, stress, plasticity and kinase/signaling genes were all down-regulated following CIS, except for the gene that codes for corticotropin releasing hormone, which was upregulated. Changes in opioid gene expression following chronic stress were limited to the CA2 and CA3 regions (lateral sample). In conclusion, modest sex- and regional-differences are seen in expression of the opioid receptor genes, as well as genes involved in stress and plasticity responses in the hippocampus following CIS.

Keywords: Corticotrophin releasing factor Delta opioid receptor Drug addiction Neural plasticity.


Chronic stress differentially alters mRNA expression of opioid peptides and receptors in the dorsal hippocampus of female and male rats

Teresa A. Milner, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Teresa A. Milner, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.

Mary Jeanne Kreek, Bruce S. McEwen, and Teresa A. Milner should be considered as co-senior authors.

Funding information: Hope for Depression Research Foundation, Grant/Award Number: none National Institute of Mental Health, Grant/Award Numbers: MH041256, MH102065 National Institute on Drug Abuse, Grant/Award Number: DA08259 National Institutes of Health, Grant/Award Numbers: HL098351, HL136520

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Abstract

Chronic immobilization stress (CIS) results in sex-dependent changes in opioid peptide levels and receptor subcellular distributions within the rat dorsal hippocampus, which are paralleled with an inability for males to acquire conditioned place preference (CPP) to oxycodone. Here, RNAScope in situ hybridization was used to determine the expression of hippocampal opioid peptides and receptors in unstressed (US) and CIS estrus female and male adult (∼2.5 months old ) Sprague Dawley rats. In all groups, dentate granule cells expressed PENK and PDYN additionally, numerous interneurons expressed PENK. OPRD1 and OPRM1 were primarily expressed in interneurons, and to a lesser extent, in pyramidal and granule cells. OPRK1-was expressed in sparsely distributed interneurons. There were few baseline sex differences: US females compared to US males had more PENK-expressing and fewer OPRD1-expressing granule cells and more OPRM1-expressing CA3b interneurons. Several expression differences emerged after CIS. Both CIS females and males compared to their US counterparts had elevated: (1) PENK-expressing dentate granule cells and interneurons in CA1 and CA2/3a (2) OPRD1 probe number and cell expression in CA1, CA2/3a and CA3b and the dentate gyrus and (3) OPRK1-expressing interneurons in the dentate hilus. Also, CIS males compared to US males had elevated: (1) PDYN expression in granule cells (2) OPRD1 probe and interneuron expression in CA2/3a (3) OPRM1 in granule cells and (4) OPRK1 interneuron expression in CA2/3a. The sex-specific changes in hippocampal opioid gene expression may impact network properties and synaptic plasticity processes that may contribute to the attenuation of oxycodone CPP in CIS males.


Chronic stress differentially alters mRNA expression of opioid peptides and receptors in the dorsal hippocampus of female and male rats

Teresa A. Milner, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA

Teresa A. Milner, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.

Mary Jeanne Kreek, Bruce S. McEwen, and Teresa A. Milner should be considered as co-senior authors.

Funding information: Hope for Depression Research Foundation, Grant/Award Number: none National Institute of Mental Health, Grant/Award Numbers: MH041256, MH102065 National Institute on Drug Abuse, Grant/Award Number: DA08259 National Institutes of Health, Grant/Award Numbers: HL098351, HL136520

Abstract

Chronic immobilization stress (CIS) results in sex-dependent changes in opioid peptide levels and receptor subcellular distributions within the rat dorsal hippocampus, which are paralleled with an inability for males to acquire conditioned place preference (CPP) to oxycodone. Here, RNAScope in situ hybridization was used to determine the expression of hippocampal opioid peptides and receptors in unstressed (US) and CIS estrus female and male adult (∼2.5 months old ) Sprague Dawley rats. In all groups, dentate granule cells expressed PENK and PDYN additionally, numerous interneurons expressed PENK. OPRD1 and OPRM1 were primarily expressed in interneurons, and to a lesser extent, in pyramidal and granule cells. OPRK1-was expressed in sparsely distributed interneurons. There were few baseline sex differences: US females compared to US males had more PENK-expressing and fewer OPRD1-expressing granule cells and more OPRM1-expressing CA3b interneurons. Several expression differences emerged after CIS. Both CIS females and males compared to their US counterparts had elevated: (1) PENK-expressing dentate granule cells and interneurons in CA1 and CA2/3a (2) OPRD1 probe number and cell expression in CA1, CA2/3a and CA3b and the dentate gyrus and (3) OPRK1-expressing interneurons in the dentate hilus. Also, CIS males compared to US males had elevated: (1) PDYN expression in granule cells (2) OPRD1 probe and interneuron expression in CA2/3a (3) OPRM1 in granule cells and (4) OPRK1 interneuron expression in CA2/3a. The sex-specific changes in hippocampal opioid gene expression may impact network properties and synaptic plasticity processes that may contribute to the attenuation of oxycodone CPP in CIS males.


A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

This article provides a simplified and standardized protocol for induction of depressive-like behavior in chronically immobilized mice by using a restrainer. In addition, behavior and physiological techniques to verify induction of depression are explained.

Begin by setting the room to light at 200 lux using a digital lux meter. House the mouse in a separate cage at least a week before testing, and place the mouse in the testing room for at least 30 minutes before the experiment. Gently hold the mouse tail to avoid tensing the mouse, and then carefully place it on a rough surface.

Cover the restrainer with a small white towel and then gently place the mouse at the opening of the restrainer, so that the mouse enters the restrainer voluntarily. Next, place the closure to restrain the mouse as tight as possible, being careful to avoid damage to the body, such as tail, feet, and testicles. Lastly, during the exposure to the restrainer, measure body weight and food intake every 48 hours.

Prior to testing, habituate the mice to the presence of two drinking bottles, one containing 0.1 molar sucrose and the other containing plain water for 48 hours. Switch the positions of the two bottles after 24 hours to reduce any confounding produced by a side bias. On the third day deprive the mice of water for 24 hours.

Then on the day of the experiment expose the mice to two drinking bottles for six hours. After three hours, switch the position of the water bottles. Record the volume in milliliters of sucrose solution and water consumed, and then calculate the animal's affinity to sucrose.

Finally, calculate sucrose preference as a percentage of the volume of sucrose consumption over the total fluid consumption during the test. Begin by bringing the chronic restraint stress induced mice into the testing room at least 30 minutes before beginning the tail suspension test. Set the room light to dim conditions at 50 lux.

Next, place the camera about 40 centimeters from the mouse. Suspend the mouse firmly from the horizontal bar using adhesive tape. After the mouse is positioned in the middle of the suspension box start recording, and observe the behavioral alterations continuously for six minutes.

If the mouse attempts to climb its tail use a stick or climb stopper to prevent it from doing so. At the end of the experiment move the mouse to its home cage and carefully remove the tape from its tail. Finally, use video tracking software to analyze the accumulated time of immobile periods.

Results indicate decrease in body weight for the CIS group and significantly less food intake at day four. Compared to controls, a decrease was shown for sucrose preference in the CIS group, while there was a significant increase in immobility time and corticosterone. Further, a glutamine supplemented diet ameliorates depressive like behaviors, as shown for body weight, food intake, sucrose preference, immobility, and corticosterone.


Influence of Xiaoyaosan on depressive-like behaviors in chronic stress-depressed rats through regulating tryptophan metabolism in hippocampus

Background: Tryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan.

Methods: Forty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods.

Results: The behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects.

Conclusion: The abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.

Keywords: IDO1 TPH2 Xiaoyaosan chronic immobilization stress depression traditional Chinese formula traditional Chinese medicine tryptophan.


Watch the video: Spinal Immobilisation: The Basics (January 2023).