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From Pathophysiology to Novel Antidepressant Drugs: Glial Contributions to the Pathology and Treatment of Mood Disorders
Open accessAbstract
Several structural and cellular changes, including marked glial anomalies, have been observed in association with major depressive disorder. Here we review these cellular alterations and highlight the importance of glial cell pathology, especially astroglial dysfunction, in the pathophysiology of neuropsychiatric disorders with a particular interest in major depressive disorder. The functional role of astrocytes in glutamate uptake and glutamate/glutamine cycling is discussed, as is the deleterious effects of chronic stress on glial cell function. Lastly, we discuss the effect of antidepressants on glial cell function and the possibility of targeting glial cells in the quest to develop novel therapeutics.
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“Several human postmortem studies have also shown reductions in the expression of several components critical to astrocyte function, largely in the mPFC, but also some evidence in the hippocampus, suggesting impaired glutamate-glutamine cycling (133).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [133]
In the citing paper
“There is also emerging evidence of impaired glutamate-glutamine cycling in the mPFC and hippocampus amongst those with MDD.”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [133]
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“Subjects with depression have been shown to display a variety of glutamatergic abnormalities, including reduced glial density, decreased expression of the glutamate reuptake transporters EAAT1 and EAAT2 and decreased enzymatic conversion from glutamate to glutamine [33].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [33]
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Metadata
- Authors
- Sanacora, G., & Banasr, M.
- Affiliations
- Yale University (US)
- Corresponding author
- Sanacora, Gerard
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 73
- Issue
- 12
- Pages
- 1172-1179
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3688253
- OpenAlex
- W2077129553
- Cited by
- 239
- References
- 102
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 14 · 2023: 17 · 2022: 17 · 2021: 22 · 2020: 15 · 2019: 20 · 2018: 21 · 2017: 18 · 2016: 17 · 2015: 27 · 2014: 24 · 2013: 4
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH085055, R01MH081211, R01 MH08055)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- glial cells, astrocytes, major depressive disorder, mood disorders, glutamate uptake, chronic stress, antidepressants, neuroinflammation
- MeSH terms
- Animals, Antidepressive Agents, Cell Communication, Humans, Neuroglia, Neurons, Mood Disorders
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