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CK2 regulates 5-HT4 receptor signaling and modulates depressive-like behavior
J Castello1, B LeFrancois1, M Flajolet2
1Department of Physiology, Pharmacology and Neuroscience, CUNY School of Medicine, New York, NY, USA.
Molecular Psychiatry
|November 22, 2017
Summary
The protein kinase CK2 regulates the 5-HT4 receptor, a potential target for rapid antidepressant effects. CK2alpha deletion in mice
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The serotonergic system is crucial for mood regulation, but traditional antidepressants have delayed effects.
- The 5-HT4 receptor is a novel target for rapid antidepressant therapies.
- CK2's role in regulating the 5-HT4 receptor in mood disorders is unknown.
Purpose of the Study:
- To investigate the role of CK2 in regulating the 5-HT4 receptor.
- To determine if CK2 affects 5-HT4 receptor function and mood-related behaviors.
- To identify the brain region mediating CK2's effects on mood.
Main Methods:
- Utilized CK2alpha knockout mouse models and AAV-mediated gene deletion in the prefrontal cortex.
- Assessed 5-HT4 receptor expression, signaling (cAMP production, ERK activation), and plasma membrane localization.
- Evaluated behavioral phenotypes related to depression and anxiety, and response to antidepressant treatment.
Main Results:
- CK2alpha ablation led to region-specific upregulation of 5-HT4 receptors in the prefrontal cortex (PFC).
- Enhanced 5-HT4 receptor signaling was observed in vitro and in vivo in CK2alpha-deficient PFC.
- Mice lacking CK2alpha in the PFC exhibited an 'anti-depressed-like' phenotype and improved antidepressant response.
Conclusions:
- CK2 modulates 5-HT4 receptor levels and signaling in the PFC.
- Enhanced 5-HT4 receptor activity in the PFC mediates antidepressant-like effects.
- Targeting CK2 could offer a strategy for developing rapid-acting antidepressants.
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