Adult neurogenesis in the olfaction bulb

描述（由申请人提供）：成年神经发生是一个终生发育过程，其中新神经元的诞生仅限于成年哺乳动物大脑中的选择性区域：齿状回（DG）的颗粒下区（SGZ）和沿着侧脑室（LV）的脑室下区（SVZ）。新产生的神经元在SVZ迁移沿着吻侧迁移途径嗅球。外界刺激包括丰富的环境活动和嗅觉刺激已被报道诱导成人神经发生。成年SVZ-嗅球轴的神经发生被假设在雌性小鼠的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，成年嗅球神经发生的调节机制仍然很大程度上不确定。ERK 5是一种促分裂原活化蛋白激酶（MAPK），来自我们实验室的数据表明，ERK 5指定皮层神经干细胞的神经元命运，并促进发育中大鼠皮层中新生成的神经元的存活。在这个建议中，我将测试的假设，ERK 5可能发挥一个新的和关键的作用，在成人神经发生的SVZ嗅球轴。确定调节嗅球中成人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：成年嗅球神经元参与嗅觉的能力目前正在探索中，然而，许多调节这一过程的分子机制尚不清楚。化学感受系统的可塑性随着年龄的增长而下降，从而阻止了对世界完整风味和气味的持续享受。确定调节成年嗅球神经元的产生和整合的分子机制可能会对神经干细胞替代策略和治疗嗅觉系统敏感性的年龄相关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.