PRENATAL DEVELOPMENT OF THE HUMAN CORTICAL SYNAPSES

人类皮质突触的产前发育

基本信息

批准号：
2034290
负责人：
NADA R ZECEVIC
金额：
$ 12.61万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-30 至 1998-08-31
项目状态：
已结题

项目摘要

The main objective of this proposal is to study prenatal synaptogenesis in the cortex of human embryos and fetuses. Formation of synapses represents a major event in the cellular differentiation of the brain and it is of the utmost importance for the subsequent development of the normal functional capacity of brain. It is generally accepted that a critical mass of synapses is necessary for the emergence of any particular cortical function and that changes in synaptic density are correlated with changes in cortical function. Furthermore, defects in fine morphological and chemical differentiation of cortical neurons during synaptogenesis may affect mental health and behavior. However, despite its importance, very little quantitative data about synaptic density in human development is available. I have chosen to focus on the Intrauterine phases of human development and to provide necessary quantitative data about early synaptic contacts which are important initial steps in the developmental cascade that results in normal cortical structure and function. To establish baseline data about human prenatal synaptogenesis three specific aims are proposed: l) to determine the synaptic density and laminar distribution of particular synaptic types (asymmetrical, symmetrical, on spines, on dendritic shafts), 2) to characterize cortical synapses by the transmitter they use, and 3) to study possible synaptic active areas using synapsin I, a molecule related to synaptogenesis. Already existing fetal cortical tissue embedded for electron microscopy will be qualitatively and quantitatively analyze"d. Additional fetal cortical tissue will be obtained and labeled with antibodies to dopamine (DA), tyrosine hydroxylase (TH), gama-aminobutyric acid (GABA), glutamate (Glu) and acetylcholine (ACh) for immuno- electron microscopy, while immunohistochemistry for synapsin I will he applied to observe development of synapses in larger blocks of human embryonic and fetal brains. We believe that this, presently missing, knowledge about synaptogenesis in human, will help us to better understand the formation of normal cortical circuitry, as well as genetic and congenital defects of the CNS.

该提案的主要目的是研究产前突触发生在人类胚胎和胎儿的皮质中。突触的形成代表大脑细胞分化和这对于随后的发展至关重要大脑的正常功能能力。人们普遍认为突触的临界质量对于任何出现都是必要的特定的皮质功能和突触密度的变化是与皮质功能的变化相关。此外，缺陷皮质神经元的细小形态和化学分化在突触发生过程中可能会影响心理健康和行为。然而，尽管它很重要，但关于突触的数量数据很少可以使用人类发展的密度。我选择专注于人类发展的宫内阶段，并提供必要关于早期突触接触的定量数据发育级联的初始步骤导致正常皮质结构和功能。建立有关人类的基线数据产前突触发生三个特定目的：l）确定特定突触的突触密度和层流分布类型（不对称的，对称的刺，树突状轴上），2）通过使用的发射器来表征皮质突触，3）使用突触I（与分子相关的突触I）研究可能的突触活动区域突触发生。已经存在的胎儿皮质组织已嵌入电子显微镜将进行定性和定量分析。将获得其他胎儿皮质组织并标记多巴胺（DA），酪氨酸羟化酶（Th），GAMA-氨基丁基的抗体免疫电子的酸（GABA），谷氨酸（GLU）和乙酰胆碱（ACH）显微镜，同时突触的免疫组织化学，我将申请观察大型人类胚胎块中突触的发展和胎儿大脑。我们认为，目前缺少的知识人类的突触发生，将帮助我们更好地理解形成正常皮质回路以及遗传和先天性缺陷中枢神经系统。