Liu H, Sankar R, Shin D H, Mazarati A M, Wasterlain C G
Epilepsy Research Laboratory, Veteran Administration Medical Center, Sepulveda, CA 91343, USA.
Neuroscience. 2000;101(2):297-304. doi: 10.1016/s0306-4522(00)00383-3.
Substance P, which modulates synaptic excitability, can be induced by a variety of stimuli. We studied the expression of hippocampal substance P in rats in using lithium-pilocarpine model of status epilepticus during development. Status epilepticus resulted in an age-specific manner of substance P expression that was anatomically distinctive in hippocampal subfields. Maximal induction of substance P immunoreactivity was seen in the CA1 region of the two-week-old rats, and progressively decreased in the three-, four-week-old rats and adults. Meanwhile, the number of substance P-immunoreactive neurons in the CA3 region and dentate granule cell layer was minimal in the two-week-old animals, but approximated the adult level in the three- and four-week-old rats. No substance P-immunoreactive axon terminals were seen in the strata pyramidale and lucidum in the CA3 region of the two-week-old rats, but they were found to progressively increase in the three-, four-week-old rats and adults. To confirm substance P expression after status epilepticus, we studied the expression of preprotachykinin-A mRNA in the hippocampus of the three-week-old rats by in situ hybridization. Two hours following injection of lithium-pilocarpine, preprotachykinin-A mRNA dramatically increased in the granule cells, as well as in the CA3 and CA1 pyramidal cell layers of the hippocampus. To evaluate the relationship between behavioral seizures and substance P induction, we used the NMDA receptor antagonist MK-801. Injection of MK-801 completely blocked lithium-pilocarpine-induced behavioral seizures and SP induction in the two-week-old rats. These results indicate that seizure activity selectively evokes age-dependent and region-selective expression of substance P.
P物质可调节突触兴奋性，可由多种刺激诱导产生。我们在发育过程中使用癫痫持续状态的锂-匹罗卡品模型研究了大鼠海马P物质的表达。癫痫持续状态导致P物质表达呈现年龄特异性方式，在海马亚区具有解剖学上的独特性。在两周龄大鼠的CA1区可见P物质免疫反应性的最大诱导，在三周龄、四周龄大鼠和成年大鼠中逐渐降低。同时，CA3区和齿状颗粒细胞层中P物质免疫反应性神经元的数量在两周龄动物中最少，但在三周龄和四周龄大鼠中接近成年水平。在两周龄大鼠的CA3区锥体层和透明层未见P物质免疫反应性轴突终末，但在三周龄、四周龄大鼠和成年大鼠中发现其逐渐增加。为了证实癫痫持续状态后P物质表达，我们通过原位杂交研究了三周龄大鼠海马中前速激肽原-A mRNA的表达。注射锂-匹罗卡品两小时后，前速激肽原-A mRNA在颗粒细胞以及海马的CA3和CA1锥体细胞层中显著增加。为了评估行为性癫痫发作与P物质诱导之间的关系，我们使用了NMDA受体拮抗剂MK-801。注射MK-801完全阻断了锂-匹罗卡品诱导的两周龄大鼠的行为性癫痫发作和P物质诱导。这些结果表明，癫痫发作活动选择性地诱发P物质的年龄依赖性和区域选择性表达。
