De Micheli E, Soncrant T T
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
Neurobiol Aging. 1992 Nov-Dec;13(6):687-95. doi: 10.1016/0197-4580(92)90091-b.
To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease.
为研究胆碱能新皮质输入随年龄变化的功能重要性，并探讨老年动物皮质胆碱能去神经支配是否能更好地模拟阿尔茨海默病的脑代谢变化，我们在年轻和老年大鼠中研究了单侧损毁大细胞基底核（NBM）对脑葡萄糖代谢的影响。采用[14C]脱氧葡萄糖法，在向右侧NBM立体定向注射鹅膏蕈氨酸后3、7、14和28天，测定3月龄和24月龄Fischer-344大鼠48个脑区的局部脑葡萄糖代谢率（rCMRglc），并在3天和14天后测定假手术动物的rCMRglc。对于两个年龄组，单侧NBM损毁的峰值效应均在3天后出现：在年轻大鼠中，所检查的全部24个前皮质区域的rCMRglc均显著降低（与对侧相比）（平均下降20%），而在老年动物中，24个区域中只有9个区域的葡萄糖利用率显著下降，且rCMRglc降低幅度（9%）较小。年轻和老年大鼠的rCMRglc在7天时几乎完全恢复。我们得出结论，基底皮质胆碱能投射在老年大鼠新皮质功能中的作用较小，可能是因为其紧张性活动降低。单侧NBM损毁后，年轻和老年大鼠的皮质代谢均恢复正常；因此，NBM损伤的老年大鼠并不是阿尔茨海默病中rCMRglc逐渐下降的更好模型。
