Kelley M S, Steward O
Department of Neuroscience, University of Virginia, Charlottesville 22908.
Int J Dev Neurosci. 1993 Apr;11(2):105-15. doi: 10.1016/0736-5748(93)90071-k.
This study evaluates whether the rapid transient increases in glial fibrillary acidic protein (GFAP) mRNA in the hippocampus after electrolytic lesions of the entorhinal cortex (EC) are triggered by lesion-induced changes in hippocampal neuronal activity (either the decreases that result from loss of afferent drive or transient increases that occur during lesion production). To evaluate the role of activity, we carried out four experiments: (1) tetrodotoxin (TTX) was injected into the EC to mimic the decreases in afferent drive that occur after lesion; (2) TTX was injected into the EC or hippocampus before producing electrolytic lesions to block any abnormal activity induced during lesion production; (3) the EC was destroyed by aspiration, thus creating a lesion comparable in size to the electrolytic lesion, without passing direct current; (4) seizures were elicited by stimulating the EC of anesthetized rats, to examine whether electrographic seizures alone can induce the same type of increases in GFAP mRNA as lesions. Our results demonstrated that: (1) TTX injections into the EC did not induce the same increases in GFAP mRNA levels that occurred after EC lesions; (2) animals that received TTX injections into the EC prior to lesions exhibited increases in hippocampal GFAP mRNA that were nearly as great as following EC lesions alone; (3) aspiration lesions of the EC resulted in increases in GFAP mRNA that were comparable to those observed after electrolytic lesions; and (4) seizure-inducing stimulation of the EC resulted in 2-fold increases in GFAP mRNA in the hippocampus 24 hr after stimulation rather than the 5-13-fold increases observed after lesions. These results suggest that lesion-induced changes in hippocampal neuronal activity are not solely responsible for inducing the rapid transient increases in GFAP mRNA levels in the hippocampus ipsilateral to EC lesions.
本研究评估了内嗅皮层（EC）电解损伤后海马中胶质纤维酸性蛋白（GFAP）mRNA的快速短暂增加是否由损伤诱导的海马神经元活动变化所触发（即传入驱动丧失导致的减少或损伤产生过程中出现的短暂增加）。为了评估活动的作用，我们进行了四项实验：（1）将河豚毒素（TTX）注入EC以模拟损伤后发生的传入驱动减少；（2）在产生电解损伤之前将TTX注入EC或海马，以阻断损伤产生过程中诱导的任何异常活动；（3）通过抽吸破坏EC，从而产生与电解损伤大小相当的损伤，而不通过直流电；（4）刺激麻醉大鼠的EC引发癫痫发作，以检查仅电图癫痫发作是否能诱导与损伤相同类型的GFAP mRNA增加。我们的结果表明：（1）向EC注射TTX并未诱导出与EC损伤后相同的GFAP mRNA水平增加；（2）在损伤前接受向EC注射TTX的动物，其海马GFAP mRNA的增加几乎与仅接受EC损伤后的增加一样大；（3）EC的抽吸损伤导致GFAP mRNA的增加与电解损伤后观察到的增加相当；（4）诱导癫痫发作的EC刺激在刺激后24小时导致海马中GFAP mRNA增加2倍，而不是损伤后观察到的5 - 13倍增加。这些结果表明，损伤诱导的海马神经元活动变化并非单独导致EC损伤同侧海马中GFAP mRNA水平的快速短暂增加。
