Ossowska K
Department of Neuro-Psychopharmacology, Polish Academy of Sciences, Kraków.
Pol J Pharmacol. 1993 Mar-Apr;45(2):109-31.
This paper reviews the changes in dopaminergic, cholinergic and glutamatergic neurotransmission, which occur in the aging of the central nervous system (CNS) and in age-related diseases: Parkinson's disease (PD) and Alzheimer's disease (AD). Dopaminergic neurotransmission is impaired with age due to degeneration of the substantia nigra pars compacta neurons and reduction of the density of postsynaptic D1 and D2 dopamine receptors in the striatum. PD is believed to be caused by a severe loss of dopaminergic neurons, which leads to nearly complete depletion of dopamine in the striatum, particularly in the putamen. The supersensitivity of postsynaptic dopamine receptors, reported by some authors, may result from compensatory mechanisms to degeneration of dopaminergic neurons. The role of aging in PD is also discussed in the paper. An interest in the role of the cholinergic and glutamatergic systems in aging results from the concept that the development of AD is due to the pathology of these systems. The data on cholinergic neurotransmission are controversial and imply that aging affects rather slightly both neurons and cholinergic receptors. In AD, however, severe degeneration of cholinergic neurons of the basal nucleus of Meynert, leading to the impairment of cholinergic neurotransmission in the hippocampus and the cerebral cortex, has been observed. In AD degeneration of glutamatergic neurons and subsensitivity of some excitatory amino acids receptors in the hippocampus and the cerebral cortex may lead to dementia. However, an increase in the glutamate release from presynaptic glutamatergic terminals may be responsible for neuronal degeneration in AD. The role of the beta-amyloid protein in a neurodegenerative activity of glutamic acid is discussed.
本文综述了多巴胺能、胆碱能和谷氨酸能神经传递的变化，这些变化发生在中枢神经系统（CNS）衰老以及与年龄相关的疾病：帕金森病（PD）和阿尔茨海默病（AD）中。由于黑质致密部神经元的退化以及纹状体中突触后D1和D2多巴胺受体密度的降低，多巴胺能神经传递随年龄增长而受损。PD被认为是由多巴胺能神经元的严重丧失引起的，这导致纹状体中多巴胺几乎完全耗尽，尤其是在壳核中。一些作者报道的突触后多巴胺受体超敏反应可能是多巴胺能神经元退化的代偿机制所致。本文还讨论了衰老在PD中的作用。对胆碱能和谷氨酸能系统在衰老中的作用的关注源于这样一种概念，即AD的发生是由于这些系统的病理变化。关于胆碱能神经传递的数据存在争议，表明衰老对神经元和胆碱能受体的影响相当轻微。然而，在AD中，已观察到Meynert基底核的胆碱能神经元严重退化，导致海马体和大脑皮层中胆碱能神经传递受损。在AD中，谷氨酸能神经元的退化以及海马体和大脑皮层中一些兴奋性氨基酸受体的亚敏感性可能导致痴呆。然而，突触前谷氨酸能终末谷氨酸释放的增加可能是AD中神经元退化的原因。本文讨论了β-淀粉样蛋白在谷氨酸神经退行性活动中的作用。
