Retchkiman I, Fischer B, Platt D, Wagner A P
Institute of Gerontology, University of Erlangen-Nürnberg, Germany.
Neurobiol Aging. 1996 Jan-Feb;17(1):41-4. doi: 10.1016/0197-4580(95)02022-5.
The molecular mechanisms associated with age-related alterations in the pharmacological and physiological properties of hippocampal and cortical neurons in response to chemically induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-colonic seizures. Using RNA gel blot analysis we found that 1 h after the onset of seizure, the mRNA for the protooncogene c-fos was increased in the hippocampus and cortex of 3-month-old rats. The levels of c-fos mRNA in the hippocampus and cortex of 3-month-old rats returned to control levels by 3 h after PTZ administration. The levels of c-fos mRNA in the hippocampus and cortex of 20-month-old and 30-month-old rats peaked at 3 h and returned to basal levels by 15 h following PTZ treatment. These results suggest that the induction of immediate-early gene expression, as exemplified by c-fos, is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure and the levels of c-fos mRNA induction are decreased by about 49% in the cortex and by 27% in the hippocampus of 30-month-old rats, as compared to the levels expressed by 3-month-old rats.
与化学诱导癫痫发作时海马体和皮层神经元药理及生理特性的年龄相关变化相关的分子机制在很大程度上尚不清楚。给不同年龄的大鼠注射戊四氮（PTZ）（50毫克/千克体重）可诱发强直性结肠癫痫发作。通过RNA凝胶印迹分析，我们发现癫痫发作开始1小时后，3月龄大鼠海马体和皮层中原癌基因c-fos的mRNA增加。PTZ给药3小时后，3月龄大鼠海马体和皮层中c-fos mRNA水平恢复到对照水平。2月龄和3月龄大鼠海马体和皮层中c-fos mRNA水平在PTZ治疗后3小时达到峰值，并在15小时后恢复到基础水平。这些结果表明，以c-fos为例的即刻早期基因表达的诱导在老年大鼠脑中并未受损。然而，老年大鼠脑对化学诱导癫痫发作的反应较慢，与3月龄大鼠表达的水平相比，3月龄大鼠皮层中c-fos mRNA诱导水平降低约49%，海马体中降低27%。
