重组腺病毒载体在大鼠海马中过表达神经肽Y能够有效抑制急性诱发癫痫的发作,延迟点燃癫痫的发生,减少癫痫发作的易感性。
此外,一些研究表明rAAV-NPY可以减少慢性癫痫模型大鼠海马的发作频率,抑制癫痫症状的恶化。《中国神经再生研究(英文版)》杂志2013年5月第14期发表的一项关于“Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain”的研究证实,以重组腺相关病毒为载体,将神经肽Y基因通过立体定向的方法转染到红藻氨酸诱发的癫痫大鼠脑内,神经肽Y可以实现在癫痫脑内的基因过表达。
基因转染后4周,大鼠的癫痫发作程度明显受到抑制,且癫痫大鼠海马内N-甲基-D-天门冬氨酸受体亚单位NR1, NR2A和NR2B的mRNA和蛋白表达受到抑制。作者认为神经肽Y基因转染有可能通过下调N-甲基-D-天门冬氨酸受体的表达发挥抗癫痫作用。(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