Adult neurogenesis in the olfaction bulb

描述(申请人提供)：成年神经发生是一个终生的发育过程，在这个过程中，新神经元的诞生被限制在成年哺乳动物大脑中的特定区域：齿状回(DG)的颗粒下区(SGZ)和侧脑室(LV)的脑室下区(SVZ)。SVZ中新生成的神经元沿着吻端迁移路径迁移到嗅球。外界刺激，包括环境丰富的活动和嗅觉刺激，已被报道诱导成人神经发生。SVZ-嗅球轴中的成年神经发生被认为在嗅觉和信息素介导的雌性小鼠的雄性优势中发挥作用。尽管有这些令人兴奋的发现，但调节成人嗅球神经发生的机制在很大程度上仍然不清楚。ERK5是一种丝裂原活化蛋白激酶(MAPK)，我们实验室的数据表明，ERK5决定了大脑皮层神经干细胞的神经元命运，并促进了发育中的大鼠大脑皮质新生神经元的存活。在这项提案中，我将检验ERK5可能在SVZ-嗅球轴中的成人神经发生中发挥新的关键作用的假设。明确成人嗅球神经发生的分子机制可能会对神经干细胞替代策略和治疗与年龄相关的嗅觉系统可塑性下降产生重大影响。 公共卫生相关性：目前正在探索成年出生的嗅球神经元促进嗅觉的能力，然而，许多调控这一过程的分子机制尚不清楚。化学感觉系统的可塑性随着年龄的增长而下降，因此无法继续享受世界的全部味道和香味。明确调控成年出生的嗅球神经元生成和整合的分子机制可能会对神经干细胞替代策略和治疗与年龄相关的嗅觉系统敏感度下降产生重大影响。

DESCRIPTION (provided by applicant): Adult neurogenesis is a life-long developmental process where the birth of new neurons is restricted to selective regions in the adult mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) and the sub-ventricular zone (SVZ) along the lateral ventricles (LV). Newly generated neurons in the SVZ migrate along the rostral migratory pathway to the olfactory bulb. External stimuli including environmental enrichment activities and olfactory stimulation have been reported to induce adult neurogenesis. Adult neurogenesis in the SVZ-olfactory bulb axis has been hypothesized to play a role in olfaction and pheromone-mediated male dominance in female mice. Despite these exciting discoveries, mechanisms mediating adult neurogenesis in the olfactory bulb are still largely undefined. ERK5 is a mitogen-activated protein kinase (MAPK) and data from our lab demonstrated that ERK5 specifies neuronal fate of cortical neural stem cells and promotes survival of newly generated neurons in the developing rat cortex. In this proposal, I will test the hypothesis that ERK5 may play a novel and critical role in adult neurogenesis in the SVZ-olfactory bulb axis. Defining the molecular mechanisms regulating adult neurogenesis in the olfactory bulb could lead to significant impacts toward neural stem cell replacement strategies and treating age-related decline in olfactory system plasticity. PUBLIC HEALTH RELEVANCE: The capability of adult-born neurons in the olfactory bulb to contribute to olfaction are currently being explored, however, many of the molecular mechanisms regulating this process are unclear. Plasticity of the chemosensory system declines with age, thus preventing the continued enjoyment of full flavors and scents of the world. Defining the molecular mechanisms regulating the generation and integration of adult-born olfactory bulb neurons could lead to significant impacts toward neural stem cell replacement strategies and treating age- related decline in olfactory system sensitivity.