Abstracts

RATIONALE: Previously we have shown that in the kainic acid model of status epilepticus-induced hippocampal cell loss, estrogen administration in physiological doses has a neuroprotective effect on hilar and CA3 neurons. This estrogen effect seems to be mediated by intracellular estrogen receptors leading to gene activation, which results in modulation of protein synthesis. We studied the effect of estrogen on neuropeptide Y (NPY) expression, which may be involved in neuroprotection. METHODS: Rats were ovariectomized one week before hormone replacement. Oil vehicle or -estradiol (2 g/day) were injected subcutaneously 48 and 24 hours prior to saline or kainic acid (16 mg/kg i.p.). Rats were behaviorally monitored for 5 hour. All rats were injected with pentobarbital (50 mg/kg i.p.) irrespective of seizure severity. The rats received two additional doses of estrogen or oil prior to sacrifice 48 hours later. Thus there were four groups: oil + KA seizures, oil + saline (no seizure), estrogen + KA seizures, estrogen + saline (no seizure). Brains were processed for NPY immunohistochemistry. RESULTS: Estrogen treatment in rats without seizures increased NPY-immunoreactivity in the hilar interneurons and mossy fibers compared to oil controls. Kainic acid status epilepticus resulted in increased NPY-immunoreactivity, which followed a different pattern in estrogen- compared to oil-treated rats. This difference was observed mostly in the hilar mossy fibers and in the granule cell layer, where the NPY was highly expressed in oil-treated rats, while in estrogen-treated animals this increase was to a lesser extent. CONCLUSIONS: Estrogen administration modulates the expression of NPY prior and after seizures. These findings indicate that the neuroprotective effects of estrogen on seizure-induced hippocampal damage may involve an interaction with NPY. Supported by NS 20253 and NS 30387.