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Astroglial Connexin43 as a Potential Target for a Mood Stabiliser
Motohiro Okada1, Tomoka Oka1, Misaki Nakamoto1
1Department of Neuropsychiatry, Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu 514-8507, Japan.
International Journal of Molecular Sciences
|January 5, 2021
Summary
Mood disorders are complex, with current treatments insufficient. New research explores the role of astroglial connexins in mood regulation, suggesting novel therapeutic targets beyond traditional monoamine-based approaches.
Area of Science:
- Neuroscience
- Psychopharmacology
- Cellular Biology
Background:
- Mood disorders, including major depressive disorder and bipolar disorder, represent significant global health challenges.
- Current pharmacotherapies, primarily targeting monoamine systems, show limitations in effectively treating these conditions.
- Emerging evidence highlights the role of glutamatergic pathways and tripartite synaptic transmission in mood disorder pathophysiology.
Purpose of the Study:
- To review the impact of psychopharmacological agents on astroglial connexins, specifically connexin43.
- To explore the complex roles of astroglial gap junctions and hemichannels in mood regulation.
- To identify gaps in current knowledge and propose future research directions for novel mood disorder treatments.
Main Methods:
- Review of preclinical findings on the effects of antidepressants, mood-stabilizing antipsychotics, and anticonvulsants on astroglial connexin expression and function.
- Analysis of the literature concerning stress-induced changes in astroglial connexin activity.
- Synthesis of current psychopharmacological progress in understanding tripartite synaptic transmission.
Main Results:
- Stressful stimuli that induce depressive moods suppress connexin43 expression and astroglial gap junction function while enhancing astroglial hemichannel activity.
- Monoamine transporter-inhibiting antidepressants reduce astroglial hemichannel activity and improve astroglial gap junction function.
- Certain mood stabilizers, distinct from antidepressants, appear to activate astroglial hemichannel activity.
Conclusions:
- Astroglial connexin function, particularly the balance between gap junctions and hemichannels, is critically involved in mood regulation.
- Current pharmacotherapies exert differential effects on astroglial connexin activity, suggesting complex mechanisms of action.
- Further research is needed to elucidate these mechanisms and develop novel therapeutic strategies targeting astroglial pathways for mood disorders.
Keywords:
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