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.
Original language | English (US) |
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Pages (from-to) | 3954-3966 |
Number of pages | 13 |
Journal | Molecular Neurobiology |
Volume | 53 |
Issue number | 6 |
DOIs | |
State | Published - Aug 1 2016 |
Keywords
- Astrocyte
- Astrogenesis
- Brain size
- GFAP
- GSK-3
- Hypertrophy
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience