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EAAT2 as a Research Target in Bipolar Disorder and Unipolar Depression: A Systematic Review
Caren J Blacker1, Vincent Millischer2,3, Lauren M Webb4
1Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, Minnesota, USA.
Molecular Neuropsychiatry
|May 14, 2020
Summary
Excitatory amino acid transporter 2 (EAAT2) dysfunction is linked to mood disorders. Reduced EAAT2 levels correlate with depression, highlighting its role in glutamate regulation and potential therapeutic targeting.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Glutamate plays a key role in the neuropathology of major depressive disorder and bipolar disorder.
- Excitatory amino acid transporter 2 (EAAT2) is the primary glutamate transporter in the brain, regulating extracellular glutamate levels and preventing excitotoxicity.
- EAAT2 is a critical target for understanding the glutamate-glutamine cycle's interaction with neuronal systems in mood disorders.
Purpose of the Study:
- To systematically review the literature on Excitatory Amino Acid Transporter 2 (EAAT2) in mood disorders.
- To elucidate the role and regulation of EAAT2 in major depressive disorder and bipolar disorder.
- To identify future research directions for EAAT2 in mood disorders.
Main Methods:
- A systematic literature search was conducted for EAAT2 studies published between January 1992 and January 2018.
- Analysis of 40 identified studies focusing on EAAT2 expression, regulation, and function in mood disorders.
- Review of findings in both rodent models and human studies.
Main Results:
- Chronic stress and steroid exposure were most frequently associated with decreased EAAT2 levels.
- Inhibition of EAAT2 in rodents exacerbated depressive behaviors.
- Human studies generally showed decreased EAAT2 expression in depression, with some regional variations.
Conclusions:
- EAAT2 is significantly implicated in the neuropathology of mood disorders, particularly depression.
- Further research is needed to explore EAAT2's role in bipolar disorder and its potential as a therapeutic target.
- Understanding EAAT2's function within glial macromolecular complexes is crucial for insights into intracellular signaling, energy regulation, and cellular homeostasis.
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