| Objective: To investigate the expression and the potential role of PSD95/NR2B on epileptogenesis in hippocampus of rats with epilepsy and to explore the effect of Ubiquitin-proteasome pathway (UPP) on the expression of PSD95/NR2B of epileptic rats.Methods: Epileptic model of wistar rats was established by pilocarpine injection intraperitoneally. The expression of PSD95/NR2B in hippocampus was examined by the immunofluorescent analysis. Then applying MG-132, the inhibitor of UPP, to pretreated experimental rats, and detect the expression changes of PSD95/NR2B comparing with PILO group. Using Histopathological stain to detect morphological changes in hippocampus, and the ethology observation was also performed at the same time.Results:1. Ethology observation: 72.22 % (26/36) of PILO-treated rats survived status epilepticus (SE), the mortality rate was 19.44%, 69.44%(25/36)of these rats developed grade V seizures, the mean incubation period (MIP) was 36.36±5.58 min. 63.89%(23 /36) of MG-132 pretreated rats survived SE, the mortality rate was 33.33 %, 91.67% ( 33/36 ) of these rats developed grade V seizures (P<0.05, VS. PILO group),the mean incubation period (MIP) was 27.27±5.04 min (P<0.05, VS. PILO group). The control rats that were treated with physiological saline didn't present any abnormal behaviors.2. Pathology observation: The neurons of all hippocampus in the control groups were line up in order, the shape of neurons were integrity. After 6h of SE, the formation of CA1, CA3 and dentate hilar were damaged and showed degeneration, necrosis and slight cell loss. After 24h of SE, the changes of all hippocampal subareas aggravated, cell loss were obvious. Compared with the pilocarpine treated rats, degeneration and necrosis of neurons in MG132 pretreated rats were more severe, cell loss became more serious.3. The expression of PSD95/NR2B: PSD95/NR2B was generally present in the hippocampus of control group. Compared with the control, the expression of PSD95/NR2B was gradually decreased in hippocampus of pilocarpine-induced epileptic rats, the decreased expression of PSD95/NR2B reached a peak at 24 h (P<0.01, VS. PILO group), and returned to basal level at 7d. The down-regulation of PSD95/NR2B expression in hippocampus had been inhibited in the MG-132 pretreated rats(P<0.05, VS. PILO group). The expression of PSD95/NR2B had no statistical significance compared with the control group. Conclusion: Li-PILO induced seizure causes a significant decrease of PSD95/NR2B expression during acute stage. Ubiquitin-proteasome pathway plays an important role in the down-regulation of PSD95/NR2B expression in hippocampus. The down-regulation of PSD95/NR2B expression is considered to be a protective mechanism in epileptogenesis. |
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