GABA receptor-mediated effects in the peripheral nervous system: A cross-interaction with neuroactive steroids
Valerio Magnaghi1, Marinella Ballabio, Antonio Consoli
1Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy. valerio.magnaghi@unimi.it
Journal of Molecular Neuroscience : MN
|April 25, 2006
Summary
Peripheral nervous system Schwann cells express GABA receptors, influencing myelin protein synthesis. Neuroactive steroids and GABA receptors interact, affecting myelin production in the peripheral nervous system.
Area of Science:
- Neuroscience
- Cell Biology
- Peripheral Nervous System Research
Background:
- Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the mammalian central nervous system (CNS).
- GABA receptors (GABAA and GABAB) are found on CNS neurons and glial cells, potentially targeted by neuroactive steroids.
- The presence and function of GABA receptors in the peripheral nervous system (PNS) remain less understood.
Purpose of the Study:
- To investigate the expression and function of GABAA and GABAB receptors in the PNS, specifically in sciatic nerve and Schwann cells.
- To determine the influence of GABA receptor ligands and neuroactive steroids on Schwann cell proliferation and myelin protein expression.
- To explore potential cross-interactions between GABAergic systems and neuroactive steroids in myelinating cells.
Main Methods:
- Utilized specific ligands like muscimol (for GABAA) and baclofen (for GABAB) to study Schwann cell responses.
- Assessed the impact of progesterone (P) metabolites, such as allopregnanolone, on myelin protein synthesis (P0 and PMP22).
- Examined the influence of P, dihydroprogesterone, and allopregnanolone on GABAB subunit expression in Schwann cells.
Main Results:
- Demonstrated that both GABAA and GABAB receptors are expressed in the sciatic nerve and myelin-producing Schwann cells.
- Showed that muscimol and baclofen modulate Schwann cell proliferation and the expression of myelin proteins P0 and PMP22.
- Confirmed that allopregnanolone, acting through GABAA receptors, affects PMP22 synthesis.
- Revealed that progesterone and its metabolites influence GABAB subunit expression in Schwann cells.
Conclusions:
- Schwann cells in the PNS express functional GABAA and GABAB receptors.
- Neuroactive steroids, particularly progesterone metabolites, interact with GABA receptors in Schwann cells.
- These findings suggest a cross-interaction within the GABAergic system in PNS myelinating cells, involving both GABA receptors and neuroactive steroids, impacting myelin production.
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