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- Title
Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function.
- Authors
Wenbin Wang; Song Lu; Tan Li; Yung-Wei Pan; Junhui Zou; Abel, Glen M.; Lihong Xu; Storm, Daniel R.; Zhengui Xia
- Abstract
Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function andhave more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury.
- Subjects
MITOGEN-activated protein kinases; DEVELOPMENTAL neurobiology; OLFACTORY bulb; LABORATORY mice; NEUROPHYSIOLOGY
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 20, p7833
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3745-14.2015