Xu Xiaoxue, Guo Feng, He Qun, Cai Xinze, Min Dongyu, Wang Qianhui, Wang Shaocheng, Tian Liu, Cai Jiqun, Zhao Yujie
Biochip Center, College of Basic Medicine, China Medical University, Shenyang 110001, China; Department of Neurology, The First Hospital of China Medical University, Shenyang 110001, China.
Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
Neuropeptides. 2014 Apr;48(2):97-105. doi: 10.1016/j.npep.2013.12.003. Epub 2013 Dec 30.
As an endogenous inhibitor of glutamate-mediated synaptic transmission in mammalian central nervous system, neuropeptide Y (NPY) plays a crucial role in regulating homeostasis of neuron excitability. Loss of balance between excitatory and inhibitory neurotransmission is thought to be a chief mechanism of epileptogenesis. The abnormal expression of NPY and its receptors observed following seizures have been demonstrated to be related to the production of epilepsy. The tremor rat (TRM) is a hereditary epileptic animal model. So far, there is no report concerning whether NPY and its receptors may be involved in TRM pathogenesis. In this study, we focused on the expression of NPY and its three receptor subtypes: Y1R, Y2R and Y5R in the TRM brain. We first found the expression of NPY in TRM hippocampus and temporal lobe cortex was increased compared with control (Wistar) rats. The mRNA and protein expression of Y1R was down-regulated in hippocampus but up-regulated in temporal lobe cortex, whereas Y2R expression was significantly increased in both areas. There was no significant change of Y5R expression in either area. The immunohistochemistry data showed that Y1R, Y2R, Y5R were present throughout CA1, CA3, dentate gyrus (DG) and the entorhinal cortex which is included in the temporal lobe cortex of TRM. In conclusion, our results showed the altered expression of NPY, Y1R and Y2R but not Y5R in hippocampus and temporal lobe cortex of TRM brain. This abnormal expression may be associated with the generation of epileptiform activity and provide a candidate target for treatment of genetic epilepsy.
作为哺乳动物中枢神经系统中谷氨酸介导的突触传递的内源性抑制剂，神经肽Y（NPY）在调节神经元兴奋性稳态中起关键作用。兴奋性和抑制性神经传递之间的平衡失调被认为是癫痫发生的主要机制。癫痫发作后观察到的NPY及其受体的异常表达已被证明与癫痫的产生有关。震颤大鼠（TRM）是一种遗传性癫痫动物模型。到目前为止，尚无关于NPY及其受体是否可能参与TRM发病机制的报道。在本研究中，我们重点关注了NPY及其三种受体亚型：Y1R、Y2R和Y5R在TRM脑内的表达。我们首先发现，与对照（Wistar）大鼠相比，TRM海马体和颞叶皮质中NPY的表达增加。Y1R的mRNA和蛋白表达在海马体中下调，但在颞叶皮质中上调，而Y2R的表达在这两个区域均显著增加。两个区域中Y5R的表达均无显著变化。免疫组化数据显示，Y1R、Y2R、Y5R存在于TRM颞叶皮质所包含的整个CA1、CA3、齿状回（DG）和内嗅皮质中。总之，我们的结果显示，TRM脑的海马体和颞叶皮质中NPY、Y1R和Y2R的表达发生了改变，但Y5R未改变。这种异常表达可能与癫痫样活动的产生有关，并为遗传性癫痫的治疗提供了一个候选靶点。
