Neuronal plasticity as investigated from a viewpoint of receptor research

最近，有人主张在一个神经元内共存两种或三种神经递质。最近，人们指出这种共存的模式可能会根据神经元的环境条件而改变，并且在个体发生过程中，一个特定的细胞可以将其产生的神经递质从一种转换到另一种。在临床上，研究神经元的潜在可塑性是阐明各种神经退行性疾病的病理生理机制的关键之一。我们研究了退行性疾病中神经递质受体的形成过程和受体的变化，并试图通过比较这些结果来分析可塑性机制。对P物质受体、毒蕈碱乙酰胆碱受体（mAChR）和降钙素基因相关肽（CGRP）进行了致瘤性研究。与其他神经肽受体一样，大鼠脑中的P物质受体在胚胎后期出现。然而，P物质受体的膜内信号系统的发育过程并非如此。对于mAChR，通过体外放射自显影术观察M1和M2各亚型受体的形成过程，发现这两种亚型受体是独立分化的。免疫组织化学研究了下脑干CGRP免疫反应性的个体发生，来自外周感觉系统的CGRP阳性输入神经纤维发育较早，而来自中枢听觉和视觉系统的CGRP阳性输入神经纤维发育较晚。CGRP受体的个体发生正在研究中。在个体发生的早期，可以假设退行性过程具有更大的可塑性。至于退行性疾病中的受体变化，研究对象包括人类帕金森病、mptp诱导的猴子帕金森病、人类脊髓小脑变性、滚动小鼠名古屋和阿尔茨海默病。研究了不同神经递质受体与脑内密度和分布的关系，并将这些结果与神经递质变化和常规神经病理结果进行了比较。少

These days, coexistence of two or three neurotransmitters within one neuron has been advocated. More recently, it has been pointed out that patterns of such coexistence may change depending on enviromental conditions of neurons and one particular cell can switch its producing neurotransmitter from one to another in the course of ontogeny. Clinically, to study the potential plasticity of neurons is one of key points to elucidate pathophysiological mechanisms of various neurodegenerative disorders. We investigated the ontogenic process of neurotransmitter receptors and receptor changes in degenerative diseases, and tried to analyse plasticity mechanisms by comparing these results. Ontogenic studies were performed on substance P receptors, muscarinic acetylcholine receptors (mAChR) and calcitonin gene-related peptide (CGRP). Substance P receptors in the rat brain came to appear in the late embryonic stage as observed in other neuropeptide receptors. Nevertheless, this was not the case wit … More h the developmental course of the intramembranous signalling system of substance P receptors. As for mAChR, the ontogenic course of each subtype of M1 and M2 was observed by means of in vitro autoradiography and it was noticed that these two subtype receptors differentiated independently. Ontogeny of CGRP immunoreactivity in the lower brainstem was immunohistochemically studied and CGRP positive input nerve fibers from peripheral sensory systems developed early, while those from central auditory and visual systems came to be observed much later. Ontogeny of CGRP receptors is under investigation. Earlier in the ontogeny, more plasticity in degenerative course can be assumed. As for receptor changes in degenerative conditions, studies were done in cases of human Parkinson's disease, MPTP-induced monkey parkinsonism, human spinocerebellar degeneration, rolling mouse Nagoya and Alzheimer's disease. Receptors of various neurotransmitters were studied in relation with density and distribution in the brain in parallel with time course of these pathological conditions and these results were compared to changes of neurotransmitters and conventional neuropathological findings. Less