Zachrisson O, Lindefors N, Brené S
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, S-171 76, Stockholm, Sweden.
Brain Res Mol Brain Res. 1998 Oct 1;60(2):291-5. doi: 10.1016/s0169-328x(98)00191-0.
Substance P (SP) can play an important role in neuronal survival. To analyze the role of SP in excitotoxicity, kainic acid (KA) was administered to rats and in situ hybridization was used to analyze the levels of the SP encoding preprotachykinin-A (PPT-A) mRNA in striatal and hippocampal subregions 1, 4, and 24 h and 7 days after KA. In striatum and piriform cortex, PPT-A mRNA peaked 4 h after KA while in hippocampus, levels peaked after 24 h. KA caused seizures and neuronal toxicity as indicated by a reduction of the number of neurons in the hippocampal CA1 subregion after 7 days. KA was later administered alone or following pretreatment with the tachykinin NK1 receptor antagonist CP-122,721-1 (0.3 mg/kg). The pretreatment decreased seizure activity and a negative correlation was found between seizure activity and survival of CA1 neurons. Conclusively, treatment with CP-122,721-1 has a seizure inhibiting property and may possibly counteract KA-induced nerve cell death in CA1.
P物质（SP）在神经元存活中可发挥重要作用。为分析SP在兴奋性毒性中的作用，给大鼠注射 kainic 酸（KA），并利用原位杂交技术分析KA注射后1、4、24小时及7天纹状体和海马亚区中编码前速激肽原-A（PPT-A）mRNA的SP水平。在纹状体和梨状皮质中，PPT-A mRNA在KA注射后4小时达到峰值，而在海马中，水平在24小时后达到峰值。KA导致癫痫发作和神经元毒性，表现为7天后海马CA1亚区神经元数量减少。随后单独注射KA或先用速激肽NK1受体拮抗剂CP-122,721-1（0.3mg/kg）预处理后再注射KA。预处理降低了癫痫发作活动，并且在癫痫发作活动与CA1神经元存活之间发现了负相关。总之，CP-122,721-1治疗具有癫痫抑制特性，并且可能抵消KA诱导的CA1神经细胞死亡。
