CORE--NEUROBIOLOGY

该核心的目的是提供在几个子项目下进行的遗传操作的表型验证。该核心将提供转基因和部分三体系的神经生物学评价，这些系是为了提供在人类21号染色体上发现的单个或多个基因的过表达而构建的。将进行行为学、组织学和神经化学研究，以确定这些基因过度表达的特定神经生物学效应，以确定哪些基因单独或组合可能导致唐氏综合征中表现出的智力迟钝或其他神经生物学结果。该核心还将提供Ts65Dn小鼠中胆碱能和多巴胺能发育的评估，并将评估Moran博士项目中药理学操作的影响。拟议的核心是对前一个方案下现有核心的重大扩展。核心的这种扩大与方案不断变化的优先事项和重点是一致的。核心有两个组成部分，利用调查人员的专门知识。行为和突触前神经化学评估将在约翰霍普金斯大学精神病学系莫兰博士的实验室进行。布鲁博士将在肯尼迪克里格研究所评估大脑形态学和免疫组织化学技术。

The purpose of this core is to provide a phenotypic validation of the genetic manipulation made under several subprojects. This core will provide neurobiological evaluations of transgenic and partial trisomic lines constructed to provide over-expression of single or multiple genes found on human chromosome 21. Behavioral, histological and neurochemical and studies will be carried out to identify the specific neurobiological effects of over-expression of these genes to determine what genes singly or in combination may account for the mental retardation or other neurobiological outcome exhibited in Down syndrome. The core will also provide an assessment of cholinergic and glutamatergic development in Ts65Dn mice and will evaluate the effects of the pharmacological manipulations in Dr. Moran's project. The proposed core represents a significant expansion from what had existed under the previous program. This expansion of the core is consistent with the changing priorities and focus of the program. The core has two components which take advantage of the expertise of the investigators. The behavioral and pre-synaptic neurochemical evaluations will be carried out in Dr. Moran's laboratory within the Department of Psychiatry at Johns Hopkins. Dr. Blue will assess brain morphology and immunohistochemical techniques at the Kennedy Krieger Institute.