MOLECULAR NEUROBIOLOGY & CHILDHOOD PSYCHOPATHOLOGY

该计划包括一个行政和科学的核心 服务于四个研究领域：（1）生化调节;（2） 神经递质受体的生物化学;（3）神经化学 犬发作性睡病的研究和（4）临床神经化学和 儿童自闭症的遗传学研究 的中心主题 儿童普遍性发育障碍 反映中枢神经系统功能障碍，具有明确的生化指标 和代谢的后果。 该计划的调查范围 范围从基因调控，蛋白质结构和 神经药理学的诊断和治疗策略 婴儿自闭症 程序的每个组成部分都与 其他项目领域，同时保留一个单独的基地， 科学探究 生化调节部分的重点是 调节儿茶酚胺生物合成酶多巴胺 s-羟化酶和苯乙醇胺N-甲基转移酶，来自 通过翻译后的事件。 的研究 它们结构、亚基组成和氨基酸序列 酶的克隆工作正在进行， 结构 这些探针和特异性抗体将用于 研究酶调节的分子事件。 的 受体部分研究5 HTIb的分子特征， 5 HTIC受体，溶解和纯化这些蛋白质， 开发分子探针来研究它们的调节。 发育研究检查大脑中的多巴胺能- 去甲肾上腺素能系统将是一个协调的努力， 和受体部分。 嗜睡症部分研究 胆碱能、多巴胺能和 犬发作性睡病中的去甲肾上腺素能系统， 也发生在儿童身上。 在感受器上工作， 参与这些系统的酶正在进行中， 努力研究它们的个体发育和遗传调控。 的 临床科积累了大量的儿童数据库， 自闭症和相关的广泛性发育障碍， 开发出了将它们分为四种类型的方法，更独特的， 同质临床组。 目前正在开展工作， 遗传、产前和生化标记与这些 亚型 最后，一个新的项目领域将研究遗传学， 在多重家庭与自闭症先证者的连锁，使用 用于鉴定限制性片段的一系列cDNA探针 多态性

This program consists of an administrative and scientific core serving four investigative areas: (1) Biochemical Regulation; (2) Biochemistry of Neurotransmitter Receptors; (3) Neurochemical Studies in Canine Narcolepsy and (4) Clinical Neurochemical and Genetic Studies in infantile autism. The central theme of the program is that pervasive developmental disorders in children reflect central nervous system dysfunction with defined biochemical and metabolic consequences. The investigative scope of the program ranges from basic work in gene regulation, protein structure and neuropharmacology to diagnostic and therapeutic strategies in infantile autism. Each component of the program interdigitate with the other project areas while retaining a separate base of scientific inquiry. The biochemical Regulation section focuses on the regulation of the catecholamine biosynthetic enzymes, dopamine s-hydroxylase and phenylethanolamine N-methyltransferase, from genomic through posttranslational events. Studies on the structure, subunit composition and amino acid sequence of these enzymes are ongoing as is work cloning cDNA probes encoding their structure. These probes and specific antibodies will be used to investigate molecular events underlying enzyme regulation. The Receptor section studies the molecular characteristics of 5HTIb and 5HTIc receptors, is solubilizing and puriFying these proteins and developing molecular probes to study their regulation. Developmental studies examining the brain serotonergic- noradrenergic system will be a coordinated effort of the Regulation and Receptor sections. The Narcolepsy section studies neurochemical deficits in the cholinergic, dopaminergic and noradrenergic systems implicated in canine narcolepsy, a genetic disorder also occurring in children. Work on the receptors and enzymes involved in these systems is underway, as are intergroup efforts studying their ontogeny and genetic regulation. The Clinical section has accumulated a large database of children with autism and related pervasive developmental disorders, and has developed methods of subtyping them into four, more distinct, homogeneous clinical groups. Work is underway to define discrete genetic, prenatal and biochemical markers associated with these subtypes. Finally, a new project area will investigate genetic linkage in multiplex families with autistic probands, using a series of cDNA probes to identify restriction fragment polymorphisms.