A mechanism for glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to metabolic insults.

摘要: Glucocorticoids appear capable of damaging or destroying hippocampal neurons. There is a progressive loss such neurons with age, and the process can be prevented by adrenalectomy at mid-age accelerated prolonged exposure to high circulating titers glucocorticoids. The present study examines possible mechanisms for this steroid action. Rats were either adrenalectomized, intact, treated corticosterone (CORT) sufficient produce elevations in physiological range. After 1 week, unilateral microinfusions made kainic acid (KA) 3-acetylpyridine (3-AP). Doses these neurotoxins chosen small-sized lesions. Treatment CORT exacerbated extent damage following neurotoxin infusion, whereas attenuated damage. Additional studies eliminated some potential phenomenon. did not directly alter intrinsic toxicity compounds but, rather, altered sensitivity target cells them. As evidence, no potentiation CORT-treated animals occurred KA-sensitive brain regions lacking receptors. Since increase diffusion binding [3H]KA hippocampus, it appears unlikely that potentiated toxin-induced influencing specific mechanism action any toxin. Finally, general nature was supported markedly different postulated KA 3-AP. We hypothesize exerts its extensive catabolic effects upon generalized metabolic vulnerability possessing concentrations receptors, thereby sensitizing them varied insults.