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Akt2 deficiency is associated with anxiety and depressive behavior in mice
Christina Leibrock1, Teresa F Ackermann, Michael Hierlmeier
1Department of Physiology I, University of Tuebingen, Germany.
Background:
The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K) / glycogen synthase 3 kinase (GSK3) signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF) effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice.
Methods:
Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze) have been performed with Akt2 knockout mice (akt(-/-)) and corresponding wild type mice (akt(+/+)).
Results:
Anxiety and depressive behavior was significantly higher in akt(-/-) than in akt(+/+) mice. The akt(-/-) mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test). Moreover, akt(-/-) mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression.
Conclusion:
Akt2 might be a key factor in the pathophysiology of depression and anxiety.
Insights
Akt2 deficiency significantly increases anxiety and depressive behaviors in mice, suggesting its crucial role in mood regulation. These findings highlight Akt2 as a potential target for treating depression and anxiety disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Major depressive disorder and anxiety disorders represent significant global health burdens.
- The precise cellular and molecular underpinnings of these conditions remain elusive.
- Akt2, a key protein in the PI3K/GSK3 pathway, influences mood and fear memory.
Purpose of the Study:
- To investigate the behavioral impact of Akt2 deficiency in mice.
- To explore the role of Akt2 in anxiety and depressive-like behaviors.
Main Methods:
- Behavioral assessments were conducted using a battery of tests.
- Akt2 knockout mice (akt(-/-)) and wild-type littermates (akt(+/+)) were utilized.
Main Results:
- Akt2 knockout mice exhibited significantly higher anxiety and depressive behaviors compared to wild-type mice.
- Cognitive functions remained intact in Akt2 knockout mice.
- Increased anxiety was observed in the O-Maze, Light-Dark box, and Open Field tests.
- Elevated immobility in the Forced Swimming Test indicated depressive-like behavior.
Conclusions:
- Akt2 plays a critical role in the pathophysiology of depression and anxiety.
- Targeting Akt2 may offer a novel therapeutic strategy for mood disorders.
