Adult neurogenesis in the olfaction bulb

描述（由申请人提供）：成人神经发生是一个终生的发育过程，其中新神经元的诞生仅限于成年哺乳动物大脑的选择性区域：齿状回（DG）的亚颗粒区（SGZ）和沿侧脑室（LV）的室下区（SVZ）。SVZ中新生成的神经元沿吻侧迁移途径向嗅球迁移。外界刺激包括环境富集活动和嗅觉刺激已被报道可诱导成人神经发生。svz -嗅球轴的成年神经发生已被假设在雌性小鼠嗅觉和信息素介导的雄性优势中发挥作用。尽管有这些令人兴奋的发现，但在嗅球中介导成人神经发生的机制在很大程度上仍然不明确。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指定皮层神经干细胞的神经元命运，并促进发育中的大鼠皮层新生成神经元的存活。在本提案中，我将验证ERK5可能在svz -嗅球轴的成人神经发生中发挥新的关键作用的假设。确定成人嗅球神经发生的调控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。

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.