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Reelin-Related Disturbances in Depression: Implications for Translational Studies
Hector J Caruncho1, Kyle Brymer2, Raquel Romay-Tallón3
1Neuroscience Cluster, College of Pharmacy and Nutrition, University of Saskatchewan Saskatoon, SK, Canada.
Frontiers in Cellular Neuroscience
|March 5, 2016
Summary
Reelin protein levels decrease in depression. This study shows reelin deficits in an animal model and human patients, suggesting reelin restoration may offer new antidepressant therapies.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Reelin expression is reduced in mood and psychotic disorders.
- Reelin regulates adult hippocampal plasticity, suggesting a role in depression pathogenesis.
Purpose of the Study:
- To investigate the role of reelin in depression using an animal model.
- To explore reelin's potential as a therapeutic target for depression.
Main Methods:
- Utilized a repeated corticosterone (CORT) injection animal model to induce depression-like symptoms.
- Examined reelin-immunopositive cells in the dentate gyrus subgranular zone (SGZ).
- Analyzed reelin co-expression with nNOS and alterations in glutamatergic/GABAergic circuits.
Main Results:
- CORT treatment decreased reelin-positive cells in the SGZ, paralleling depression-like phenotypes.
- Reelin downregulation altered reelin/nNOS co-expression and neurotransmitter circuit balance.
- Antidepressant co-treatment prevented reelin deficits and depression-like symptoms.
- Observed altered lymphocyte membrane protein clustering in animals and human patients, correlating with therapeutic response.
Conclusions:
- Reelin deficits are linked to depression pathogenesis.
- Restoring reelin function presents a novel therapeutic strategy for depression.
- Lymphocyte membrane protein clustering may predict antidepressant treatment response.
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