Hicks T P, Conti F
Department of Psychology, College of Arts and Sciences, University of North Carolina at Greensboro 27412, USA.
Can J Physiol Pharmacol. 1996 Apr;74(4):341-61.
A number of different factors contributed to the rationale for providing a critical review of the field of excitatory amino acids in the cerebral cortex at this time. In addition to the recent growing realisation by clinicians that the excitatory amino acids are linked critically to a number of neurological conditions, including neurodegenerative syndromes such as Alzheimer's disease, cortical damage due to stroke and cerebral ischemia, epilepsy, amyotropic lateral sclerosis, and schizophrenia, the recent cloning and membrane reconstitution of specific receptors known as AMPA, NMDA, kainate, and metabotropic receptors and their known subunits have prompted a surge of renewed interest in this important family of synaptic transmitter molecules. Moreover, recent advances in our understanding of the molecular events involved in growth promotion in the early stages of the development of the cortex have shown that both NMDA and non-NMDA receptor subtypes perform important roles in certain aspects of target selection and neurite outgrowth, in cone stimulation and guidance, and in spine formation and morphological alterations. A recent explosive growth in interest in the possible roles of nitric oxide and related short-lived radicals in plasticity, disease, and synaptic transmission also is related closely with the actions of excitatory amino acids. All these relatively new advances have transpired in parallel with ongoing work that has extended our appreciation for the roles of excitatory amino acids in the areas of synaptic plasticity (long-term potentiation, long-term depression, receptive field reorganisation following drug-induced or peripheral sensory disturbances, such as denervation or amputation), in processes of normal transmission at functionally and electrophysiologically identified neurones of the cerebral cortex, and in distinct proposed roles for cortical glia. A greater appreciation of the diverse types and properties of the burgeoning family of receptors for the metabotropic receptor also contributed to our desire to feature that aspect of the field in the context of glia and neurones of the cerebral cortex. That part of the field of neuroscience concerned with the functions of excitatory amino acids has grown so large over the past 10 years or so, that a review paper focusing on the contributions to a specialized meeting devoted solely to cerebral cortex could easily be supported by material comprising a sufficient body of communications from top-quality research laboratories. The present account endeavours to summarize and discuss the biochemical characteristics, physiological roles, pharmacological properties, clinical relevance, developmental involvements, and anatomical-morphological aspects pertaining to the excitatory amino acid transmitters in cerebral cortex.
目前,有多种不同因素促成了对大脑皮质中兴奋性氨基酸领域进行批判性综述的合理性。除了临床医生最近越来越认识到兴奋性氨基酸与许多神经系统疾病密切相关,包括神经退行性综合征如阿尔茨海默病、中风和脑缺血导致的皮质损伤、癫痫、肌萎缩侧索硬化症和精神分裂症外,最近对称为AMPA、NMDA、海人藻酸和代谢型受体及其已知亚基的特定受体进行的克隆和膜重组,引发了对这一重要的突触传递分子家族的新一波兴趣热潮。此外,我们对皮质发育早期生长促进过程中涉及的分子事件的最新认识表明,NMDA和非NMDA受体亚型在靶点选择和神经突生长、锥体刺激和导向以及棘突形成和形态改变的某些方面都发挥着重要作用。最近,人们对一氧化氮和相关短寿命自由基在可塑性、疾病和突触传递中可能发挥的作用的兴趣呈爆发式增长,这也与兴奋性氨基酸的作用密切相关。所有这些相对较新的进展都与正在进行的工作同时出现,这些工作扩展了我们对兴奋性氨基酸在突触可塑性(长期增强、长期抑制、药物诱导或外周感觉障碍如去神经支配或截肢后感受野重组)、大脑皮质功能和电生理鉴定的神经元正常传递过程以及皮质胶质细胞的不同假定作用等领域作用的认识。对代谢型受体这一新兴受体家族的不同类型和特性有了更深入的了解,也促使我们希望在大脑皮质胶质细胞和神经元的背景下突出该领域的这一方面。在过去大约10年里,神经科学中与兴奋性氨基酸功能相关的领域发展得如此之大,以至于一篇专注于对专门针对大脑皮质的一次专题会议贡献的综述文章,很容易就能得到来自顶级研究实验室足够数量的通讯材料的支持。本报告旨在总结和讨论与大脑皮质中兴奋性氨基酸递质相关的生化特征、生理作用、药理特性、临床相关性、发育参与情况以及解剖形态学方面。