重組腺病毒載體在大鼠海馬中過表達(dá)神經(jīng)肽Y能夠有效抑制急性誘發(fā)癲癇的發(fā)作,延遲點燃癲癇的發(fā)生,減少癲癇發(fā)作的易感性,。
此外,一些研究表明rAAV-NPY可以減少慢性癲癇模型大鼠海馬的發(fā)作頻率,,抑制癲癇癥狀的惡化?!吨袊窠?jīng)再生研究(英文版)》雜志2013年5月第14期發(fā)表的一項關(guān)于“Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain”的研究證實,,以重組腺相關(guān)病毒為載體,將神經(jīng)肽Y基因通過立體定向的方法轉(zhuǎn)染到紅藻氨酸誘發(fā)的癲癇大鼠腦內(nèi),,神經(jīng)肽Y可以實現(xiàn)在癲癇腦內(nèi)的基因過表達(dá),。
基因轉(zhuǎn)染后4周,大鼠的癲癇發(fā)作程度明顯受到抑制,,且癲癇大鼠海馬內(nèi)N-甲基-D-天門冬氨酸受體亞單位NR1, NR2A和NR2B的mRNA和蛋白表達(dá)受到抑制,。作者認(rèn)為神經(jīng)肽Y基因轉(zhuǎn)染有可能通過下調(diào)N-甲基-D-天門冬氨酸受體的表達(dá)發(fā)揮抗癲癇作用。(生物谷Bioon.com)
doi:10.3969/j.issn.1673-5374.2013.14.007
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Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain
Changzheng Dong1 , Wenqing Zhao1, 2 , Wenling Li 2 , Peiyuan Lv3 , Xiufang Dong4
Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors