Neuropeptide Y exerts neuroprotective function to an animal model of genetic epilepsy: Tremor rat associated with abnormal changes in Calmodulin/Calmodulin-dependent Protein Kinase Ⅱ

Xiaoxue Xu  Jingmei Zhang  Qianhui Wang  Zhi Li  Dongyi Zhao  Jianing Li  Feng Guo  
【摘要】:Neuropeptide Y(NPY) is an endogenous neuropeptide which is recognized as an important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. It is believed to be closely related to epileptogenesis and could act as an endogenous anticonvulsant peptide, but the precise mechanism is unknown. The tremor rat(TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. In our previous research, we discovered the elevated expression of NPY in TRM brains and speculated that the internal NPY neuroprotective system may still work to some extent in TRM, but the amount of NPY seems still not sufficient to avoid epileptogenesis for TRM. Therefore, in the present study, we administrated exogenous NPY to TRM by intracerebroventricular injection in order to observe the potential neuroprotection exerted by this neuropeptide. The frequency as well as duration of TRM seizures, measured by EEG, have both significantly decreased after injecting NPY for three days compared with saline injection. The data from Morris water maze test concluded that NPY could also improve the learning and memory impairments in TRM. Additionally, the declined calmodulin(Ca M) and increased pcalmodulin-dependent Protein Kinase II(p-Ca MKII) expression have been detected in TRM hippocampus from NPY treatment groups by Western blot. In sum, our results firstly disclosed the neuroprotective effect of NPY on a genetic epilepsy animal model: TRM, suggesting that NPY might be employed as a possible therapy to hereditary seizures. Moreover, Ca M/Ca MKII pathway may be involved in this NPY protective effect.
【作者单位】:Department of Neurology, the First Hospital of China Medical University Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University
【基金】:supported by the National Natural Science Foundation Committee of China(81471323) college students'innovative entrepreneurial training program in Liaoning province(2015039)
Neuropeptide Y exerts neuroprotective function to an animal model of genetic epilepsy: Tremor rat associated with abnormal changes in Calmodulin/Calmodulin-dependent Protein Kinase Ⅱ@Xiaoxue Xu$Department of Neurology, the First Hospital of China Medica

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