title: Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.
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 and have 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.
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: Song
authors.initials: S
authors.lastname: Lu
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, Department of Biochemistry and Genetics, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Tan
authors.initials: T
authors.lastname: Li
authors.affiliation: Graduate Program in Molecular and Cellular Biology, and.
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Pan
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zou
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195.
authors.forename: Glen M
authors.initials: GM
authors.lastname: Abel
authors.affiliation: Department of Biochemistry and Genetics, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, Washington 98195.
authors.forename: Daniel R
authors.identifier: http://orcid.org/0000-0003-2149-6079
authors.initials: DR
authors.lastname: Storm
authors.affiliation: Toxicology Program, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, Graduate Program in Molecular and Cellular Biology, and zxia@u.washington.edu.
authors.forename: Zhengui
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D012903:Smell
chemical_list: D048054:Mitogen-Activated Protein Kinase 7
keywords: ERK5; MAP kinase; adult neurogenesis; olfaction