Adrenal steroids mediate the increase of hippocampal nerve growth factor biosynthesis following bicuculline convulsions.
Northern blot analysis of nerve growth factor (NGF) messenger ribonucleic acid (mRNA), together with a two-site enzyme immunoassay for NGF protein, showed that a convulsive dose of bicuculline (0.4 mg/kg, IV) induced a rapid (within 1 hour) three-fold increase in hippocampal NGF mRNA. This increase was followed by a significant increase in NGF protein 5 hours later. No changes were detected in the cerebral cortex. The increase of rat hippocampal NGF mRNA and protein content was associated with an increase in plasma corticosterone content. Both responses were completely prevented by a pretreatment with diazepam (5 mg/kg, IP), which suggested that adrenal steroids might be a stimulus underlying the rapid increase in NGF biosynthesis following bicuculline convulsions. Therefore, we tested to determine whether a convulsive dose of bicuculline could increase NGF mRNA in adrenalectomized and sham-operated rats. Bicuculline increases hippocampal NGF mRNA in sham-operated rats, but not in adrenalectomized rats despite the presence of convulsions in both experimental groups. Moreover, in adrenalectomized rats, dexamethasone (0.5 mg/kg, SC) could partly restore the increase in hippocampal NGF mRNA content induced by bicuculline convulsions; thus, adrenal steroids might have an essential role in the induction of hippocampal NGF biosynthesis elicited by bicuculline convulsions.
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Fidia-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, DC.
Costa
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Mocchetti
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D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001640:Bicuculline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015152:Blotting, Northern; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D003907:Dexamethasone; D003975:Diazepam; D003345:Corticosterone; D001640:Bicuculline