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Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice
Rebecca Kinsler1, Mary Morgan Taylor, Natasha M Flores
1Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
Abstract:
Evidence from a variety of sources suggests that structural alterations in the brain, including neurogenesis, may play a role in both the pathogenesis of mood disorders and the mechanism of action of antidepressants. Previous studies have implicated both the transforming growth factor-beta (TGF-beta), and the phosphatidyl inositol-3 kinase (PI3K)-Akt pathways in the neurogenesis-promoting and behavioral properties of antidepressants. Forkhead box protein G1 (FoxG1) is a major regulator of both of these pathways, and FoxG1 heterozygous null mice (FoxG1+/-) have previously been reported to have deficits in adult hippocampal neurogenesis and behavioral abnormalities including deficits in contextual fear learning. However the role of FoxG1, if any, in the response to antidepressants has not been previously investigated.To investigate the role of the FoxG1 gene in the behavioral and neurogenic properties of antidepressants, we tested FoxG1+/- mice and littermate controls in two different rodent models of antidepressant action: the tail suspension test and the forced swim test. FoxG1+/- mice showed no response to antidepressants in either of these tests. These results suggest that normal levels of FoxG1 may be required for the behavioral response to antidepressants.
Insights
Normal Forkhead box protein G1 (FoxG1) levels are essential for antidepressant efficacy. Mice lacking one FoxG1 gene copy showed no behavioral response to antidepressants, suggesting FoxG1
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Brain structural alterations, including neurogenesis, are implicated in mood disorders and antidepressant action.
- Transforming growth factor-beta (TGF-beta) and PI3K-Akt pathways are linked to antidepressant effects on neurogenesis and behavior.
- Forkhead box protein G1 (FoxG1) regulates these pathways and its deficiency causes neurogenesis deficits and behavioral abnormalities.
Purpose of the Study:
- To investigate the role of the FoxG1 gene in the behavioral and neurogenic responses to antidepressants.
- To determine if FoxG1 is necessary for antidepressant efficacy.
Main Methods:
- Tested FoxG1 heterozygous null mice (FoxG1+/-) and littermate controls.
- Utilized two rodent models of antidepressant action: the tail suspension test and the forced swim test.
Main Results:
- FoxG1+/- mice exhibited no behavioral response to antidepressants in either the tail suspension test or the forced swim test.
- Control mice showed typical antidepressant responses.
Conclusions:
- Normal FoxG1 levels appear to be required for the behavioral effects of antidepressants.
- These findings highlight FoxG1 as a potential factor in antidepressant treatment response.
