Abstracts

Estrogen administration in physiological doses has a neuroprotective effect on hilar and CA3c neurons in the kainic acid model of status epilepticus (SE)-induced hippocampal cell loss. This effect is associated with estrogen-induced enhancement of inhibition within the dentate gyrus by regulation of hilar neuropeptide Y (NPY) expression. To test the role of NPY in the neuroprotection, the extent of SE-induced damage was examined following blockade of the NPY system in adult ovariectomized female rats with estrogen reaplacement.
Rats were ovariectomized. A week later they were implanted intracerebroventricularly and connected to an ALZET pump filled with anti-NPY antibody (1:5). Controls received normal rabbit serum. Estradiol (2 [micro]g/day) treatment started following 24 hours subcutaneously for four days. SE was induced by kainic acid (16 mg/kg i.p.). SE was terminated with pentobarbital (50 mg/kg i.p.) following 4 hours. The rats were sacrificed 48 hours later. SE-induced damage was assessed by Fluoro Jade B staining. To determine the spread of anti-NPY antibody, immunohistochemistry omitting the primary antibody was performed. Rats with failure of anti-NPY antibody infusion served as additional controls.
Seizure threshold or severity of seizures were not affected by anti-NPY antibody infusion. In anti-NPY antibody infused rats, many degenerating neurons were detected in the hilus and CA3c hippocampal regions compared to only few Fluoro Jade B labeled neurons in controls or rats with failure of the anti-NPY antibody infusion.
The data indicates that the neuroprotective effects of estrogen on SE-induced hippocampal damage may be at least in part mediated via an interaction with NPY.
[Supported by: NS 20253, NS 30387 and Heffer Family Medical Foundation]