Aging and Neurogenesis

衰老与神经发生

• 批准号: 6899743
• 负责人: Kunlin Jin
• 金额: $ 45.04万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899743
• 关键词: age difference; aging; animal old age; behavior test; brain mapping; bromodeoxyuridine; cell differentiation; cell migration; cell proliferation; cerebral ischemia /hypoxia; dentate gyrus; histology; immunocytochemistry; laboratory rat; mature animal; nerve stem cell; neurogenesis; neuropharmacology; neurotrophic factors; stroke; voltage /patch clamp

DESCRIPTION (provided by applicant): Aging is associated with a striking increase in the incidence of stroke and neurodegenerative diseases, which are major causes of disability among those aged 70 years and older in the United States. Despite progress in understanding molecular mechanisms of neuronal cell death in these diseases, widely effective treatment remains elusive. Exciting new prospects for human stem cell therapy have been raised by the observation that neurogenesis continues to occur throughout life in the rostral subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus in the adult brain, including aged brain. However, whether the capacity for neurogenesis and the fate of newborn neural cells remain the same or change in aged brain, and whether the neurons produced actually contribute to functional recovery of the aged brain after cerebral injury are unclear. Clarification of these issues will give us a better understanding of the biology of endogenous stem/progenitor cells in aged brain and more insight into the potential of cell therapy for age-related diseases such as ischemic stroke and neurodegenerative disorders. The following specific aims will be addressed: 1. Explore whether endogenous neurogenesis is increased, decreased or unchanged in aged compared to young adult and middle-aged rats after focal cerebral ischemia and determine the regional and temporal profiles of neurogenesis after focal cerebral ischemia in vivo. 2. Determine the destinations of newly generated neural stem/progenitor cells from SVZ and SGZ of the hippocampal dentate gyrus in young adult, middle-aged and aged rat brain after ischemia. 3. Establish whether administration of the same or different neurogenesis factors promotes neurogenesis in aged compared to young adult and middle-aged rat brain and improves functional outcome after focal cerebral ischemia in vivo. 4. Determine whether neuronal cells that migrate from SVZ and SGZ develop mature phenotypic neuronal features and exhibit functional properties of neurons in young adult, middle-aged and aged rat brain after focal cerebral ischemia in vivo.

描述（由申请人提供）：衰老与中风和神经退行性疾病的发生率的显着增加有关，这是美国70岁及以上残疾的主要原因。尽管在了解这些疾病中神经元细胞死亡的分子机制方面的进展，但广泛有效的治疗仍然难以捉摸。通过观察到，神经发生在成人大脑（包括年龄脑）的鼻齿状回旋中，神经发生在整个生命中持续发生，这使人的干细胞疗法令人兴奋的新前景。但是，神经发生能力和新生神经细胞的命运是否保持不变或变化，而陈年大脑的变化以及产生的神经元是否实际上有助于脑损伤后老年大脑的功能恢复。对这些问题的澄清将使我们更好地了解老年大脑中内源性茎/祖细胞的生物学，并更多地了解与年龄相关疾病（例如缺血性中风和神经退行性疾病）的细胞治疗潜力。 将解决以下具体目标： 1。探索与局灶性脑缺血后的年轻人和中年大鼠相比，老年人的内源性神经发生是否增加，减少或不变，并确定体内局灶性脑缺血后神经发生的区域和时间特征。 2。确定来自缺血后年轻人，中年和老化大鼠脑的海马齿状回的SVZ和SGZ的新产生的神经茎/祖细胞的目的地。 3。确定与年轻的成年和中年大鼠大脑相比，相同或不同的神经发生因子的给药是否促进了老年人的神经发生，并改善体内局灶性脑缺血后的功能结果。 4。确定从SVZ和SGZ迁移的神经元细胞是否发展成熟的表型神经元特征，并在体内局灶性脑缺血后的年轻人，中年和老年大鼠大脑中神经元具有功能性能。