CORTICAL ABNORMALITIES IN A MODEL OF DOWN SYNDROME

描述：(摘自申请者的摘要)本研究的目的 程序是为了研究大脑皮层的发育 节段性16三体(Ts65Dn)小鼠--一种潜在的唐氏综合征动物模型 (DS，21三体)。在DS中复制的许多相同的21号染色体基因是 在Ts65Dn中也是三倍的，因此，DS和Ts65Dn共享共同的基因 反常现象。DS和Ts65Dn都存在空间学习和记忆缺陷 这与额叶皮质的功能损伤相一致。然而， 有关额叶发育的信息很少。 Ts65Dn中的皮层。研究人员假设，空间学习和 Ts65Dn中的记忆缺陷是由于世代中的异常， 胎儿期和/或早期神经元的成熟和存活 出生后新皮质发育。拟议中的实验探索了这种行为 在发育中的新皮质中有神经母细胞和年轻的有丝分裂后神经元。 在神经发生时期，神经元出生并迁移到其最终的 地点和连接的形成开始了。发生异常情况 在此期间可能导致古岩层的延迟形成和 大脑皮层连接。在出生后的早期生命中，突触形成， 神经元之间的连接牢固地建立起来，额外的神经元被移除 通过程序性细胞死亡。在此期间的异常可能会导致 树突状细胞组织和突触发生异常，连接丢失和 不适当的程序性细胞死亡。神经母细胞增殖缺陷， 新皮质中的突触发生、连接和程序性细胞死亡 发育可能会导致永久性的皮质异常，导致 Ts65Dn的认知缺陷。人类大脑发育中的类似缺陷可能 导致DS患者的认知缺陷。

DESCRIPTION: (adapted from applicant's abstract) The goal of this research program is to investigate the development of the cerebral cortex of the segmental trisomy 16 (Ts65Dn) mouse, a potential animal model of Down syndrome (DS, trisomy 21). Many of the same chromosome 21 genes triplicated in DS are also triplicated in Ts65Dn and therefore, DS and Ts65Dn share a common genetic abnormality. Both DS and Ts65Dn have deficits in spatial learning and memory that are consistent with functional impairment in the frontal cortex. However, there is little information available about the development of the frontal cortex in Ts65Dn. The investigators hypothesize that the spatial learning and memory deficits in Ts65Dn are due to abnormalities in the generation, maturation, and survival of neurons during prenatal neuronogenesis and/or early postnatal neocortical development. The proposed experiments probe the behavior of neuroblasts and young postmitotic neurons in the developing neocortex. During the neuronogenic period, neurons are born and migrate to their final locations and the formation of connections begins. Abnormalities occurring during this period could lead to delayed formation of the pallial layers and cortical connections. During early postnatal life, synapses are formed, interneuronal connections are firmly established, and extra neurons are removed by programmed cell death. Abnormalities during this period could lead to abnormal dendritic organization and synaptogenesis, loss of connections and inappropriate programmed cell death. Defects in neuroblast proliferation, synaptogenesis, connectivity, and programmed cell death during neocortical development could lead to permanent cortical abnormalities responsible for the cognitive deficits in Ts65Dn. Similar defects in human brain development could lead to cognitive deficits in DS.