Selective disruption of hippocampal dentate granule cells in autism: impact of PT

项目总结/摘要 在儿童的发育过程中，大多数脑细胞在出生前就已产生。有一组 然而，脑细胞在婴儿期大量产生。这发生在大脑的一个区域 称为海马体。这些细胞对于记忆、认知和大脑的正常发育 这些细胞的破坏存在于自闭症儿童中。破坏这些 细胞也可能导致自闭症儿童癫痫的患病率。虽然它使 感觉到这些细胞负责自闭症的关键特征，患有这种疾病的儿童表现出 大脑其他部位也发生了变化。我们对哪些变化是 但不幸的是，这一重要问题减缓了这一领域的进展。因此，在本提案中，我们将 研究消除已知与自闭症有关的基因对这些晚期产生的 细胞这些研究将揭示选择性地破坏这些细胞是否可以重现 自闭症证明这些细胞在自闭症的发展中起着重要作用（或 相关疾病，如癫痫），将提供一个令人信服的理由，以开发新的疗法， 保护这些脆弱的细胞。此外，由于这些细胞在发育后期出生， 实际上是在童年和成年期产生的， 自闭症诊断后产生的细胞，从而使大脑自然恢复。是我们 我希望这些研究将使我们更接近开发新的和更有效的治疗方法， 自闭症

Project Summary/Abstract During the development of a child, most brain cells are generated before birth. There is one group of brain cells, however, that are generated in large numbers in infancy. This occurs in a brain region called the hippocampus. These cells are important for the normal development of memory, cognition and language, and disruption of these cells is present in children with autism. Disruption of these cells may also contribute to the prevalence of epilepsy in children with autism. Although it makes sense that these cells are responsible for key features of autism, children with the disease exhibit changes in many other parts of the brain as well. Our limited understanding of which changes are important, unfortunately, has slowed progress in the field. In the present proposal, therefore, we will examine the impact of eliminating a gene known to be involved in autism on these late-generated cells. These studies will reveal whether selectively disrupting these cells can reproduce features of autism. Demonstrating that these cells play an important role in the development of autism (or associated conditions like epilepsy), will provide a compelling rationale to develop new therapies to protect these vulnerable cells. In addition, since these cells are born so late in development, and are actually produced through childhood and into adulthood, it may be possible to prevent the disruption of cells born after a diagnosis of autism and thus allow the brain to naturally restore itself. It is our hope that these studies will move us closer to developing new and more effective treatments for autism.