Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
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5-alpha Reductase Inhibitors
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Animals
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Cholesterol Side-Chain Cleavage Enzyme / metabolism*
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Enzyme Inhibitors / pharmacology
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Epilepsy, Temporal Lobe / enzymology
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Epilepsy, Temporal Lobe / metabolism*
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Finasteride / pharmacology
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Hippocampus / cytology
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Hippocampus / enzymology
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Immunohistochemistry
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Male
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Neuroglia / cytology
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Neuroglia / enzymology
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Neurons / enzymology
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Pilocarpine
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Rats
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Rats, Sprague-Dawley
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Status Epilepticus / chemically induced
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Status Epilepticus / enzymology
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Status Epilepticus / metabolism*
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Steroids / metabolism*
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Time Factors
Substances
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5-alpha Reductase Inhibitors
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Enzyme Inhibitors
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Steroids
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Pilocarpine
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Finasteride
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Cholesterol Side-Chain Cleavage Enzyme
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3-Oxo-5-alpha-Steroid 4-Dehydrogenase