Yufu F, Egashira T, Yamanaka Y
Department of Pharmacology, Oita Medical University, Japan.
Jpn J Pharmacol. 1994 Oct;66(2):247-55. doi: 10.1254/jjp.66.247.
To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-dependent high affinity choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H]-QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed. [3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vmax values of ChAT and AChE also decreased about 20-30% compared with those of young rats. The sodium-dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 microM-10 nM, but choline uptake in aged brain was insensitive to hemicholinium-3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons.
为了评估在自然衰老过程中是否有任何退行性变化影响大脑胆碱能系统，我们比较了老年（24个月）和年轻（2个月）大鼠大脑皮质（CR）和皮质下（SS）区域中各种胆碱能生化标志物（毒蕈碱受体数量，mAChR；胆碱乙酰转移酶活性，ChAT；乙酰胆碱酯酶活性，AChE；以及钠依赖性高亲和力胆碱摄取）。使用[3H]-喹核醇基苯甲酸酯（[3H]-QNB）作为毒蕈碱受体结合的配体，与年轻大鼠相比，老年大鼠CR和SS中mAChR的数量均减少了约30%，同时观察到mAChR的亲和力随年龄显著增加。哌仑西平能显著置换年轻和老年大鼠脑中的[3H]-QNB结合，而低浓度阿托品就能置换老年大鼠脑SS中的[3H]-QNB结合。与年轻大鼠相比，ChAT和AChE的Vmax值也降低了约20%-30%。从老年大鼠脑制备的粗突触体组分中钠依赖性高亲和力胆碱摄取低于年轻脑。半胱氨酸-3在1 microM-10 nM的浓度范围内抑制年轻大鼠脑的胆碱摄取，但老年脑的胆碱摄取对半胱氨酸-3不敏感。这些结果表明，自然衰老导致胆碱能神经元中各种生化标志物的弥漫性和多重性耗竭。
