Ogawa N, Asanuma M, Kondo Y, Nishibayashi S, Mori A
Department of Neuroscience, Okayama University Medical School, Japan.
Brain Res. 1994 Sep 26;658(1-2):87-92. doi: 10.1016/s0006-8993(09)90013-0.
Differences in the acetylcholine (ACh)-mediated neuronal system of the brain between aged and young rats were studied by measuring choline acetyltransferase (ChAT) activity, muscarinic M1 receptor (M1-R) and their respective mRNA levels. In aged rats, ChAT activity and the M1-R level were significantly reduced in the cerebral cortex, hippocampus and striatum compared with that in young rats. On the other hand, there was no difference in the ChAT mRNA level in the striatum and the basal forebrain, or the M1-R mRNA level in the cerebral cortex, hippocampus and striatum between aged and young rats. The effects of chronic administration of bifemelane (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride), which is used for the treatment of sequelae of cerebrovascular diseases, were also evaluated. In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum. However, the ChAT mRNA level and the M1-R mRNA level were not affected by bifemelane administration. Thus, the decreases and recoveries in ChAT activity and M1-R level did not parallel the changes in their respective mRNAs. These results suggest that the age-related impairments in ACh-mediated neuronal system are considered to be caused primarily by disorders of post-transcriptional events.
通过测量胆碱乙酰转移酶（ChAT）活性、毒蕈碱M1受体（M1-R）及其各自的mRNA水平，研究了老年大鼠和年轻大鼠大脑中乙酰胆碱（ACh）介导的神经元系统的差异。与年轻大鼠相比，老年大鼠大脑皮层、海马体和纹状体中的ChAT活性和M1-R水平显著降低。另一方面，老年大鼠和年轻大鼠在纹状体和基底前脑的ChAT mRNA水平，或大脑皮层、海马体和纹状体的M1-R mRNA水平上没有差异。还评估了用于治疗脑血管疾病后遗症的比芬美兰（4-(2-苄基苯氧基)-N-甲基丁胺盐酸盐）长期给药的效果。在长期给予比芬美兰的老年大鼠中，大脑皮层和海马体中的ChAT活性恢复到年轻大鼠的水平，大脑皮层、海马体和纹状体中的M1-R水平完全恢复。然而，ChAT mRNA水平和M1-R mRNA水平不受比芬美兰给药的影响。因此，ChAT活性和M1-R水平的降低和恢复与它们各自mRNA的变化并不平行。这些结果表明，ACh介导的神经元系统中与年龄相关的损伤主要被认为是由转录后事件紊乱引起的。
