Extracellular Signal-regulated Kinase 5 (ERK5) Mediates Prolactin-stimulated Adult Neurogenesis in the Subventricular Zone and Olfactory Bulb |
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Authors: | Wenbin Wang Yung-Wei Pan Tomasz Wietecha Junhui Zou Glen M. Abel Chay T. Kuo Zhengui Xia |
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Affiliation: | From the ‡Toxicology Program in the Department of Environmental and Occupational Health Sciences.;§Graduate Program in Molecular and Cellular Biology, and ;the ¶Department of Pathology, University of Washington, Seattle, Washington 98195 and ;the ‖Departments of Cell Biology and Pediatrics, Duke University, Medical Center, Durham, North Carolina 27710 |
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Abstract: | Prolactin-stimulated adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) mediates several reproductive behaviors including mating/pregnancy, dominant male pheromone preference in females, and paternal recognition of offspring. However, downstream signaling mechanisms underlying prolactin-induced adult neurogenesis are completely unknown. We report here for the first time that prolactin activates extracellular signal-regulated kinase 5 (ERK5), a MAP kinase that is specifically expressed in the neurogenic regions of the adult mouse brain. Knockdown of ERK5 by retroviral infection of shRNA attenuates prolactin-stimulated neurogenesis in SVZ-derived adult neural stem/progenitor cells (aNPCs). Inducible erk5 deletion in adult neural stem cells of transgenic mice inhibits neurogenesis in the SVZ and OB following prolactin infusion or mating/pregnancy. These results identify ERK5 as a novel and critical signaling mechanism underlying prolactin-induced adult neurogenesis. |
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Keywords: | Cell Signaling ERK MAP Kinases (MAPKs) Neurogenesis Prolactin Adult Neurogenesis ERK5 MAPK |
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