Morphological Study Of Effects Of Estrogen On GABA And P₃₈ In The Hippocampus Of PTZ-induced Epileptic Rats

Epilepsy is a group of temporarily mal-runctional Chronic disorders which results from repeated discharges of neurons in central nervous system, and which are characterized by spontaneously recurrent and refractory seizures. Some women with epilepsy showed paticular vulnerability to seizures during menstruation and ovulation, which is named catamenial epilepsy. The mechanisms on catamenial epilepsy show that ovarian steroid hormones not only regulate reproductive behavior but also exert short-term and long'-term effects on the brain. Estrogen may induce structural and functional changes in hippocampal neurons, which might increase significantly seizure susceptibility .GABA( Y -aminobutyric acid) is the most important inhibiting neurotransmitter in the brain, which plays a great role in regulating feed-back inhibition of granular cell. Studies show GABA had close relationship with epilepsy. P38(synaptophysin) is a membrane-bound protein in presynaptic element, almost in all nervous terminals. The quantity of P38 increases with synaptic growth, so the change of immnoreactive products of P38 indicates the changes of synaptic distribution and density .In this study, estrogen-replace therapy was used ,and epileptic seizures were induced by PTZ in ovaiectomized SD female rats. Immunoreactive products were observed on GABA and P38 in different brain areas of dorsal hippocampus of rats and then quantitative image analysises were made by HP I AS image analysis system.The purpose of present study was to supply the morphological basis on the mechanisms that estrogen enhances epileptic seizures.The results showed : 1) behavior observation: latent period of seizures was shortened significantly and the duration of seizures was prolonged in E2 treated groupcompared with PTZ treated group . 2) Results of GABA immonohistochemistry:GABA positive neurons significantly decreased in hilus of dorsal hippocampus of OVX rats in PTZ treated groups as compared with central groups.There was also significantly decrease of GABA positive neurons in E2 treated groups as compared with PTZ treated groups. 3)Immunoreactive products of P38 observation: immunoreaction products presented specific spot-shaped or grain-shaped. In stratum oriens and stratum radiatum of CA, area and stratum lucidum of CA3,the immunoactive intensities had no significant changes in control group compared with PTZ treated group and stronger in E2 treated group compared with PTZ treated group. However,that of molecular layer of dentate gyms had no significant changes among three groups.Conclusion: 1) behavior observation indicated that estrogen enhanced significantly epileptic seizures .2) estrogen reduced the quantity of GABA in hilus area of dorsal hippocampus,thereby lowered the inhibiting ability of GABA on epileptic seizure, and enhanced epileptic seizures sensibility.3)estrogen increased the contents of P38 in stratum oriens and stratum radiatum of CA, and stratum lucidum of CA3 (which meaned the increase of synaptic density ) .That increased the release of excitable neurotransmitters which enhanced the excitability in hippocampus.That might be one of the mechanisms of estrogen effects on the enhancement of epileptic susceptibility.