Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

GABA and myelination

A new unction for GABAA receptors has been discovered, with likely consequences for the prevention and treatment of age-related myelin abnormalities. Schwann cells express GABAA receptors and the modulation of their activity plays an important role expression of the peripheral myelin protein PMP22.

The stimulatory effects of 3a,5a-tetrahydroprogesterone and of 3a,5a-tetrahydrotestosterone (3adiol) on the PMP22 gene can indeed be mimicked by the selective GABAA receptor agonist muscimol and blocked by the selective antagonist bicuculline. How Schwann cell GABAA receptors regulate myelination still needs to be elucidated.

3a,5a-tetrahydroprogesterone also promotes myelination via the modulation of GABAA receptors within the CNS, as shown in cerebellar explant cultures of P7-rats. However, although the modulation of GABAA receptors by 3a,5a-tetrahydroprogesterone obviously plays a role in myelination, binding of PROG to its intracellular receptor appears to be required, as the promyelinating effects of progestins were completely blocked by the progesterone receptor antagonist RU486 and as progesterone had no effect on myelin formation in cerebellar slices from PRKO mice.

One mechanism by which the activation of GABAA receptors by 3a,5a-tetrahydroprogesterone may accelerate myelination in the brain is the stimulation of oligodendrocyte progenitor proliferation. This neurosteroid increased the proliferation of ePSA-NCAM+ neural progenitors grown in "oligospheres" via membrane GABAA receptors.

Reported by

University of Milano
Via Balzaretti 9
20133 Milano
Italy
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