title: Extracellular signal-regulated kinase 5 (ERK5) mediates prolactin-stimulated adult neurogenesis in the subventricular zone and olfactory bulb.
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.
authors.affiliation: Toxicology Program in the Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wang
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Pan
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wietecha
authors.forename: Junhui
authors.initials: J
authors.lastname: Zou
authors.forename: Glen M
authors.initials: GM
authors.lastname: Abel
authors.forename: Chay T
authors.initials: CT
authors.lastname: Kuo
authors.forename: Zhengui
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D013629:Tamoxifen; D011388:Prolactin; D048054:Mitogen-Activated Protein Kinase 7