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Ageing of peripheral nerves

Age-related changes in peripheral nerves mainly affect the myelinated fibers. Messenger and protein levels of the major peripheral myelin proteins P0 and PMP22 were found to be decreased during ageing.

In the sciatic nerves of old rats, treatment with 5a-dihydroprogesterone increased P0 mRNA levels, both progesterone and 5a-dihydroprogesterone increased P0 protein and the administration of 3a, 5a-tetrahydroprogesterone increased PMP22 protein. In contrast to progestins, androgens did not affect neither P0 nor PMP22 expression in the sciatic nerve of aged rats.

Progesterone is not only involved in the control of myelination in peripheral nerves, but also in axon maintenance.

The prolonged administration of progestins allowed the reversal of age-related structural abnormalities of the peripheral myelin sheaths. The systemic treatment of old male rats with progesterone, 5a-dihydroprogesterone or 3a,5a-tetrahydroprogesterone significantly decreased the percentage of fibers with myelin abnormalities and the number of fibers with irregular shapes and it increased the number of small myelinated fibers. Consistent with the finding that androgens did not affect P0 or PMP22 expression, their administration was also inefficient in reversing the myelin abnormalities. This is the first demonstration that age-relate abnormalities of myelin sheaths can be reversed by chronic treatment with neurosteroids.

Activation of the mitochondrial benzodiazepine receptor (MBR) is also able to exert beneficial effects on ageing-associated degeneration of the rat sciatic nerve. These findings thus support the potential role of MBR agonists to prevent aging-associated peripheral nerve degeneration.

Reported by

University of Milano
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20133 Milano
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