Effects Of Progesterone On GABA And MAP2 In The Hippocampus Of PTZ-induced Epileptic Rats

Laboratory and clinical studies suggested that progesterone reduced epileptic seizure activities. The mechanisms underlying this effect are not known. But there are increasing clinical and experimental evidences, which showed that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. Furthermore, limbic regions, especially hippocampus where is the target region of progesterone exists binding sites for sex steroids. Hippocampus is a key brain structure in the generation and propagation of seizure activities. The excitability of hippacampal circuit is associated with seizure activities. There are some experimental data .which showed that progesterone might affect structure and function of the hippocampus. The present study determined the effects of progesterone on pentylenetetrazol(PTZ)-induced seizures and neurons of the hippocampus in ovariectomized femal rats and helped to elucidate the mechanisms of progesterone against epilepsy seizure susceptibility.Ovariectomized (OVX) adult female Sprague-Dayley rats were divided randomly into three groups. Two control groups were designed. One group of OVX rats were injected matched doses of vehicle, normal saline(NS), intraperitoneally(i.p.) ( OVX+NS+NS group). The second one received matched doses vehicle given 0.5 h prior to PTZ treatment(OVX+NS+PTZ group). The progesterone-treated group of OVX rats were injected progesterone once per day for three days given 0.5 h prior to PTZ treatment(OVX+P+PTZ group). Convulsive responses were scored. Slices(40 μ m thick) were cut coronally using a vibratome. The slices with largest dorsal hippocampus were used for immunohistochemistry of γ -aminobutyric acid (GABA) and microtubule associated protein 2 (MAP2), respectively. Results of immunohistochemistry were analyzed by light microscope and computer analysis system.Pretreatment with the progesterone completely protected OVX females against PTZ-induced seizures, while OVX+NS+PTZ group of rats all exhibited stage 4 or 5 seizures. This suggested that P treatment significantly raised the thresholds of PTZ-induced seizures and had a significant anticonvulsive effect in adult female rats. GABA immunohistochemistry showed that the number of GABA positive neurons were significantly decreased in Hilus of NS+PTZ group as compared with OVX+NS+NS group(P<0.05). However, in OVX+P+PTZ group , the number of GABA positive neurons were significantly increased than those of OVX+NS+NS group(P<0.05) and OVX+NS+PTZ group(P<0.01). MAP2 immunohistochemistry showed that MAP-IR were decreased in Hilus, molecular layer of dendate gyrus and CA1 of OVX+NS+PTZ group as compared with NS+NS group. However, compared with those of NS+NS group and NS+PTZ group, MAP-IR were increased in OVX+P+PTZ group. These results supplied evidences that P might enhance MAP2 . This might be one of mechanisms of P's anticonvulsant effects and protective action.