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Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy.

Biagini G, Baldelli E, Longo D, Pradelli L, Zini I, Rogawski MA, Avoli M

Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy. gbiagini@unimore.it

Neurosteroids modulate seizure susceptibility, but their role in the regulation of epileptogenesis is unknown. Status epilepticus (SE) induces temporal lobe epileptogenesis following a latent period in which glial cells are activated. Here, we found that P450scc, the rate-limiting enzyme in steroid synthesis, is upregulated in hippocampal glia during the latent period after pilocarpine-induced SE in rats. More prolonged SE was associated with greater P450scc expression and longer latencies to the development of seizures, suggesting that enhanced steroid synthesis retards epileptogenesis. The 5alpha-reductase inhibitor finasteride, which blocks neurosteroid synthesis, reduced the latent period, indicating that glia-derived neurosteroids may be antiepileptogenic.

Published 15 September 2006 in Exp Neurol, 201(2): 519-24.
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