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A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors
Prerana Shrestha1, Awni Mousa1, Nathaniel Heintz1
1Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
Abstract:
Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic-pituitary-adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression.
Insights
Wfs1 gene deletion in medial prefrontal cortex layer 2/3 pyramidal cells impairs stress resilience. This dysfunction contributes to major depressive disorder (MDD) by affecting the stress response and neurotrophic factors.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Major depressive disorder (MDD) is a common mental illness often triggered by stress.
- Wfs1 gene mutations are linked to MDD in Wolfram syndrome patients.
- The medial prefrontal cortex (mPFC) plays a role in depression and resilience, but specific cell types involved are unclear.
Purpose of the Study:
- To investigate the role of Wfs1 in medial prefrontal cortex (mPFC) layer 2/3 pyramidal cells in stress-induced depressive behaviors.
- To identify specific mPFC cell types and circuits that moderate depressive behaviors in response to stress.
Main Methods:
- Utilized genetic deletion of Wfs1 in layer 2/3 pyramidal cells of the mPFC.
- Assessed stress-induced depressive behaviors.
- Measured hypothalamic-pituitary-adrenal (HPA) axis activity.
- Analyzed the accumulation of growth and neurotrophic factors.
Main Results:
- Deletion of Wfs1 in mPFC layer 2/3 pyramidal cells impaired the suppression of stress-induced depressive behaviors.
- This genetic alteration led to hyperactivation of the HPA axis.
- Altered accumulation of key growth and neurotrophic factors was observed.
Conclusions:
- Superficial layer 2/3 pyramidal cells in the mPFC are critical for moderating stress responses in the context of depressive behaviors.
- Wfs1 dysfunction in these specific cells may underlie the connection between stress and depression.
- These findings offer potential therapeutic targets for MDD.
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