Neurobiology Program, Garvan Institute of Medical Research, Sydney, Australia.
Eur Neuropsychopharmacol. 2010 Mar;20(3):164-75. doi: 10.1016/j.euroneuro.2009.08.004. Epub 2009 Sep 24.
The anticonvulsive properties of neuropeptide Y (NPY) are opening up opportunity for the development of NPY gene transfer as a therapy for epilepsy. In order to pursue the potential clinical translation of this approach, the effects of somatic NPY gene transfer on other hippocampal functions need to be assessed. The present study characterized the behavioral effects of recombinant adeno-associated viral vector (rAAV)-mediated hippocampal NPY overexpression in adult male mice and also Y1 receptor knockout mice. In wild-type mice, there were no obvious adverse effects on the general health, motor function and cognition following rAAV-NPY treatment. Moreover, hippocampal NPY overexpression induced a moderate anxiolytic effect in the open field test and elevated plus maze. Intriguingly, the treatment also increased depressive-like behavior in the tail suspension test. Elevated hippocampal NPY levels in the absence of Y1 signalling had no effects on anxiety or cognition and actually improved the depressive-like phenotype observed in the wild-type mice treated with rAAV-NPY.
神经肽 Y（NPY）的抗惊厥特性为开发 NPY 基因转移作为癫痫治疗方法提供了机会。为了推进这种方法的潜在临床转化，需要评估躯体 NPY 基因转移对其他海马功能的影响。本研究描述了重组腺相关病毒载体（rAAV）介导的成年雄性小鼠海马 NPY 过表达的行为效应，以及 Y1 受体敲除小鼠的行为效应。在野生型小鼠中，rAAV-NPY 处理后，其一般健康、运动功能和认知均未受到明显不良影响。此外，海马 NPY 过表达在旷场试验和高架十字迷宫中诱导出适度的抗焦虑作用。有趣的是，该治疗还增加了悬尾试验中的抑郁样行为。在没有 Y1 信号的情况下，升高的海马 NPY 水平对焦虑或认知没有影响，实际上改善了 rAAV-NPY 处理的野生型小鼠中观察到的抑郁样表型。
