Adrenal Steroids Mediate the Increase of Hippocampal Nerve Growth Factor Biosynthesis Following Bicuculline Convulsions

Abstract

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.

The polo-like protein kinases Fnk and Snk associate with a Ca2+- and integrin-binding protein and are regulated dynamically with synaptic plasticity

“…Neither PTZ nor KA affected Plk expression, which was undetectable in brain (not shown). Seizure effects on Fnk and Snk kinase expression were not influenced by adrenalectomy (not shown), thereby demonstrating that corticosterone released during the seizure episode (Sun et al ., 1993) does not account for the changes in gene expression described here.…”

CAAT/Enhancer-binding Protein δ and cAMP-response Element-binding Protein Mediate Inducible Expression of the Nerve Growth Factor Gene in the Central Nervous System

“…The brain was removed, and brain areas were dissected on ice, frozen on dry ice, and stored at Ϫ80°C until further processing. NGF mRNA levels in mice were determined by Northern blot analysis as previously described (34,35). In brief, total RNA was extracted and size-fractionated by agarose/formaldehyde gel electrophoresis.…”

“…Relative levels of NGF mRNA are expressed as arbitrary units and were calculated by measuring the optical density of the NGF mRNA band on the autoradiograph analyzed by a densitometer (Bio-Rad GS-710, Bio-Rad) normalized to cyclophilin, as previously described (19,35). Several exposure times were used to keep the signal intensity in a linear range.…”

Activity‐dependent and hormonal regulation of neurotrophin mRNA levels in brain–implications for neuronal plasticity

“…Thus, adrenalectomy greatly reduces the ability of kainic acid to induce NGF and BDNF mRNA in hippocampus ( Barbany and Persson, 1993;Sun et al, 1993). Furthermore, dexamethasone and kainic acid have an additive or even synergistic effect on NGF mRNA but not on BDNF mRNA levels in hippocampus ( Barbany and Persson, 1993).…”