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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Corticosterone regulates pERK1/2 map kinase in a chronic depression model
Shannon L Gourley1, Florence J Wu, Jane R Taylor
1Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, USA.
Annals of the New York Academy of Sciences
|January 6, 2009
Summary
Stress impacts mood by altering brain signaling pathways. Antidepressants may restore extracellular signal-regulated kinase 1/2 (ERK1/2) levels in the hippocampus, potentially improving depressive symptoms.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Intracellular signaling in the hippocampus is linked to depression and antidepressant efficacy.
- Extracellular signal-regulated kinase 1/2 (ERK1/2) is a key signaling molecule downstream of various receptors, influencing mood.
- Stress-induced changes in neurotrophic factors may underlie depressive symptoms.
Purpose of the Study:
- To investigate the role of ERK1/2 signaling in a novel mouse model of depression.
- To examine the effects of corticosterone exposure and antidepressant treatment on hippocampal and prefrontal cortex signaling.
- To identify potential molecular mechanisms underlying stress-related depressive symptoms and antidepressant action.
Main Methods:
- Utilized a novel, antidepressant-sensitive mouse model of depression induced by corticosterone exposure.
- Assessed motivated behavior and sucrose consumption as measures of depressive-like symptoms.
- Quantified the levels of phosphorylated ERK1/2 (pERK1/2) in specific hippocampal subregions (dentate gyrus, CA1, CA3) and the prefrontal cortex.
Main Results:
- Corticosterone exposure decreased motivated behavior, sucrose consumption, and pERK1/2 levels in the dentate gyrus.
- pERK1/2 levels were not significantly altered in the CA1 or CA3 regions of the hippocampus.
- Prefrontal cortical targets also showed regulation following corticosterone exposure.
- Antidepressant treatment appeared to restore hippocampal pERK1/2 levels after stress-induced insult.
Conclusions:
- Hippocampal ERK1/2 signaling, particularly in the dentate gyrus, is sensitive to stress and involved in depressive-like behavior.
- Antidepressants may exert their effects by restoring stress-impaired hippocampal pERK1/2 signaling.
- Prefrontal neurotrophic factors may play a significant role in the development of depressive symptoms.
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