Effects of neuropeptide Y gene transfection on seizure in rat and the expression of phosphorylated Tau protein in the rat hippocampus / 中华行为医学与脑科学杂志

ABSTRACT

Objective To discuss the effect of gene transfection of rAAV2/1-NPY-EGFP on KA-induced rat seizures,EEG and the expression of hippocampal phosphorylated Tau protein.Methods Altogether 72 healthy male Wistar adult rats were randomly divided into three groupscontrol group,KA group and NPY group(n=24).The epileptic models were established by the injection of KA 2 μl (0.4 μg/μl) five times to the right side of the hippocampus CA3 area every three days.rAAV2/1-NPY-EGFP group,in which 10 μl of rAAV2/1-NPY-EGFP (titer 5× 1011 v.g./ml) was injected to the lateral ventricle in successful rats chronic model,while KA group was injected with an equal dose of saline.The control group was injected with an equal dose of saline both in the hippocampal CA3 area and the lateral ventricle.The seizure situation,the onset latency and EEG were observed at 2 weeks and 4 weeks after vector injection.Then the expression of phosphorylated Tau protein in hippocampus were detected with Western blotting.Results (1) Scale and latency of each seizure onset in rats of rAAV2/1-NPY-EGFP group (12.13 ± 8.06) had no significant difference at 2 weeks (P＞ 0.05) compared with KA group (12.10± 8.07).The scale of seizure in rats of rAAV2/1-NPY-EGFP group(6.06±3.78) significantly reduced at 4 weeks(P ＜0.05).Latency of seizure onset (79.06±8.83min) significantly increased at 4 weeks(P＜0.05),EEG epileptic discharge frequency and wave amplitude decreased (P＜ 0.05) at 4 weeks.The control group had no seizures.(2)Compared with the control group,the expression of phosphorylated Tau protein in KA group and NPY group significantly increased(P＜0.05) at 2 weeks and 4 weeks,and the expression of phosphorylated Tau protein in the NPY group (1.15±0.16 RQ value) at 4 weeks significantly decreased (P＜0.05) compared with the KA group(1.87± 0.23 RQ value).Conclusion rAAV2/1-NPY-EGFP gene transfection significantly reduces scale of seizure onset and prolongs latency of seizure onset in KA-induced rat model.rAAV2/1-NPY-EGFP gene transfection may play anti-epileptic and neuroprotective effects through inhibiting the expression of phosphorylated Tau protein in hippocampus of KA-induced epileptic rat model.