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- Title
Isoform-specific roles for AKT in affective behavior, spatial memory, and extinction related to psychiatric disorders.
- Authors
Wong, Helen; Levenga, Josien; LaPlante, Lauren; Keller, Bailey; Cooper-Sansone, Andrew; Borski, Curtis; Milstead, Ryan; Ehringer, Marissa; Hoeffer, Charles
- Abstract
AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/ AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to neuropsychiatric disorders. Because sex is a determinant of these disorders but poorly understood, sex was an experimental variable in our design. Our studies revealed AKT isoform- and sex-specific effects on anxiety, spatial and contextual memory, and fear extinction. In Akt1 mutant males, viral-mediated AKT1 restoration in the prefrontal cortex rescued extinction phenotypes. We identified a novel role for AKT2 and overlapping roles for AKT1 and AKT3 in long-term memory. Finally, we found that sex-specific behavior effects were not mediated by AKT expression or activation differences between sexes. These results highlight sex as a biological variable and isoform- or cell type-specific AKT signaling as potential targets for improving treatment of neuropsychiatric disorders.
- Subjects
SPATIAL memory; MENTAL illness; LONG-term memory; NEUROBEHAVIORAL disorders; AFFECT (Psychology)
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.56630