title: Loss of GSK-3 Causes Abnormal Astrogenesis and Behavior in Mice.
abstract: Altered activity of glycogen synthase kinase-3 (GSK-3) is associated with psychiatric diseases and neurodegenerative diseases. GSK-3 is a key regulator in multiple aspects of neuronal differentiation in the brain. However, little is known about the role of GSK-3 in astrocyte development. To examine the role of GSK-3 in astrocytes, we generated a conditional knockout mouse using a glial fibrillary acidic protein (GFAP)-cre driver, in which the GSK-3 alpha and beta genes are deleted in astrocytes. We found that GFAP-cre-mediated GSK-3 deletion led to a larger brain. The number and size of astrocytes were increased in GSK-3 mutant brains. The levels of GFAP and phospho-STAT3, indicators of astrogenesis, were elevated in GSK-3 mutants. Furthermore, we found upregulation of astrocyte regulatory molecules such as phospho-AKT, phospho-S6, and cyclin D in GSK-3 mutant brains. Finally, GSK-3 mutant mice exhibited aberrant anxiety and social behavior. Our results suggest that GSK-3 plays a significant role in astrocyte development and behavioral control in mice.
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Eui-Man
authors.initials: EM
authors.lastname: Jung
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Minhan
authors.initials: M
authors.lastname: Ka
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA. wooyang.kim@unmc.edu.
authors.forename: Woo-Yang
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology / Q000473:pathology; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D017353:Gene Deletion; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006984:Hypertrophy; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D055495:Neurogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D053148:Caspase 3
keywords: Astrocyte; Astrogenesis; Brain size; GFAP; GSK-3; Hypertrophy