Togashi H, Kimura S, Matsumoto M, Yoshioka M, Minami M, Saito H
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Stroke. 1996 Mar;27(3):520-5; discussion 525-6. doi: 10.1161/01.str.27.3.520.
We investigated age-related changes in the central cholinergic systems in stroke-prone spontaneously hypertensive rats (SHRSP) to examine whether the regional and progressive cholinergic changes occur and are correlated with behavioral changes in the passive avoidance task.
Tissue levels of choline (Ch) and acetylcholine (ACh) were determined in the cerebral regions, including the hippocampus, of SHRSP (at two ages: 15 to 20 and 30 to 40 weeks) that had been tested in a passive avoidance task and were compared with those of age-matched controls, Wistar-Kyoto rats (WKY). With the use of in vivo microdialysis, high K+-stimulated release of hippocampal ACh, a functional parameter of the cholinergic system, was also determined in 15- to 20-week-old SHRSP.
We found that 15- to 20-week-old SHRSP demonstrated a markedly lower level of hippocampal Ch than age-matched WKY. The decrease in the Ch level in 15- to 20-week-old SHRSP was observed in all regions examined; however, in the hippocampus a significant difference from WKY was subsequently observed at the age of 30 to 40 weeks. The hippocampal ACh release was markedly decreased by repetitive stimulation with high K+ in 15- to 20-week-old SHRSP. Behavioral impairment in the passive avoidance task was observed in the two age groups of SHRSP, with significant and positive correlations between the hippocampal ACh levels and the response latency.
A decrease in hippocampal Ch level was observed in both 15- to 20-week-old and 30- to 40-week-old SHRSP, accompanied by performance failure in the passive avoidance task. The abnormal release of hippocampal ACh in response to the repetitive K+ stimulation was also noted in 15- to 20-week-old SHRSP. Thus, cholinergic dysfunction in the hippocampal system may be responsible for behavioral abnormality in the passive avoidance task in SHRSP.
我们研究了易患中风的自发性高血压大鼠（SHRSP）中枢胆碱能系统的年龄相关变化，以检验是否存在区域性和渐进性胆碱能变化，以及这些变化是否与被动回避任务中的行为变化相关。
在已进行被动回避任务测试的SHRSP（两个年龄组：15至20周和30至40周）的大脑区域（包括海马体）中测定胆碱（Ch）和乙酰胆碱（ACh）的组织水平，并与年龄匹配的对照品系Wistar-Kyoto大鼠（WKY）进行比较。使用体内微透析技术，还测定了15至20周龄SHRSP海马体中高钾刺激下ACh的释放，这是胆碱能系统的一个功能参数。
我们发现，15至20周龄的SHRSP海马体Ch水平明显低于年龄匹配的WKY。在15至20周龄的SHRSP中，在所检查的所有区域均观察到Ch水平下降；然而，在海马体中，随后在30至40周龄时观察到与WKY有显著差异。15至20周龄的SHRSP在高钾重复刺激下海马体ACh释放明显减少。在两个年龄组的SHRSP中均观察到被动回避任务中的行为损伤，海马体ACh水平与反应潜伏期之间存在显著正相关。
在15至20周龄和30至40周龄的SHRSP中均观察到海马体Ch水平下降，同时伴有被动回避任务表现不佳。在15至20周龄的SHRSP中还注意到海马体ACh对重复钾刺激的异常释放。因此，海马体系统中的胆碱能功能障碍可能是SHRSP被动回避任务中行为异常的原因。
