CORTICAL ABNORMALITIES IN A MODEL OF DOWN SYNDROME

描述：（改编自申请人摘要）本研究的目标 计划是调查大脑皮层的发展， 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，许多相同的21号染色体基因是三重的， 在Ts65Dn中也是三重的，因此，DS和Ts65Dn具有共同的遗传 异常DS和Ts65Dn在空间学习和记忆方面均存在缺陷 与额叶皮层的功能受损相一致然而，在这方面， 关于锋面发展的信息很少 Ts65Dn.研究人员假设，空间学习和 Ts65Dn的记忆缺陷是由于世代异常， 成熟和存活的神经元在产前神经元发生和/或早期 出生后新皮质发育拟议的实验探讨的行为 神经母细胞和年轻的有丝分裂后的神经元在发展中的新皮层。 在神经元发生期，神经元出生并迁移到它们的最终位置。 位置和连接的形成开始。异常发生 在此期间，可能导致套膜层的延迟形成， 皮层连接在出生后的早期，突触形成， 神经元间的连接被牢固地建立起来，多余的神经元被移除， 程序性细胞死亡在这段时间内的中断可能会导致 异常的树突组织和突触发生，连接丢失， 不适当的程序性细胞死亡神经母细胞增殖缺陷， 新皮质发育过程中的突触发生、连接和程序性细胞死亡 发展可能会导致永久性的皮质异常， Ts65Dn的认知缺陷。人类大脑发育中的类似缺陷可能 导致DS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.