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.
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.
|Li, Tan; Pan, Yung-Wei; Wang, Wenbin et al. (2013) Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb. PLoS One 8:e61948|
|Wang, Wenbin; Pan, Yung-Wei; Wietecha, Tomasz et al. (2013) Extracellular signal-regulated kinase 5 (ERK5) mediates prolactin-stimulated adult neurogenesis in the subventricular zone and olfactory bulb. J Biol Chem 288:2623-31|
|Li, Tan; Wang, Wenbin; Pan, Yung-Wei et al. (2013) A hydroxylated metabolite of flame-retardant PBDE-47 decreases the survival, proliferation, and neuronal differentiation of primary cultured adult neural stem cells and interferes with signaling of ERK5 MAP kinase and neurotrophin 3. Toxicol Sci 134:111-24|
|Pan, Yung-Wei; Zou, Junhui; Wang, Wenbin et al. (2012) Inducible and conditional deletion of extracellular signal-regulated kinase 5 disrupts adult hippocampal neurogenesis. J Biol Chem 287:23306-17|
|Pan, Yung-Wei; Kuo, Chay T; Storm, Daniel R et al. (2012) Inducible and targeted deletion of the ERK5 MAP kinase in adult neurogenic regions impairs adult neurogenesis in the olfactory bulb and several forms of olfactory behavior. PLoS One 7:e49622|
|Pan, Yung-Wei; Chan, Guy C K; Kuo, Chay T et al. (2012) Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. J Neurosci 32:6444-55|
|Zou, Junhui; Pan, Yung-Wei; Wang, Zhenshan et al. (2012) Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants. J Neurosci 32:4118-32|
|Pan, Yung-Wei; Storm, Daniel R; Xia, Zhengui (2012) The maintenance of established remote contextual fear memory requires ERK5 MAP kinase and ongoing adult neurogenesis in the hippocampus. PLoS One 7:e50455|