Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy.
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.
Biagini
Giuseppe
G
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy. gbiagini@unimore.it
Baldelli
Enrica
E
Longo
Daniela
D
Pradelli
Luca
L
Zini
Isabella
I
Rogawski
Michael A
MA
Avoli
Massimo
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology / Q000378:metabolism*; D018120:Finasteride / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000166:cytology / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism*; D013997:Time Factors
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D013256:Steroids; D010862:Pilocarpine; D018120:Finasteride; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase