Vannucchi M G, Goldman-Rakic P S
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11475-9. doi: 10.1073/pnas.88.24.11475.
In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans.
对组织切片进行的体外放射自显影以及对皮质膜匀浆进行的受体测定显示，在老年恒河猴（猕猴）的前额叶皮质和其他皮质区域，哌仑西平高亲和力毒蕈碱位点（M1）的亲和力降低。卡巴胆碱竞争实验在老年猴子中仅检测到一类单一的低亲和力位点，而在年轻成年猴子中观察到两类位点（低亲和力和高亲和力）。老年猴子中亲和力的变化并未伴随着这些位点密度的降低，此外，M1位点亲和力与年龄相关的下降是可逆的。在Mg2+存在的情况下，老年猴子中的M1毒蕈碱受体能够形成卡巴胆碱高亲和力位点。这些结果为大脑皮质中受体活性的年龄依赖性功能变化提供了证据，并表明这些受体保持一定程度的可塑性，这可能是旨在治疗老年人类记忆障碍研究的一个战略目标。
