ArticleJournal of psychiatry & neuroscience : JPN2013
Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.
Article in Journal of psychiatry & neuroscience : JPN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 4 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Glial Markers of Suicidal Behavior in the Human Brain-A Systematic Review of Postmortem Studies.International journal of molecular sciences · 2024Pooled it
- Glial Cell Abnormalities in Major Psychiatric Diseases: A Systematic Review of Postmortem Brain Studies.Molecular neurobiology · 2022Pooled it
- The Association Between Antidepressant Effect of SSRIs and Astrocytes: Conceptual Overview and Meta-analysis of the Literature.Neurochemical research · 2021Pooled it
- Peripheral blood neurotrophic factor levels in children with autism spectrum disorder: a meta-analysis.Scientific reports · 2021Pooled it
- A longitudinal PET study on changes in brain norepinephrine transporter availability following duloxetine treatment in major depressive disorder.The international journal of neuropsychopharmacology · 2025Trial
- The Gut Microbiota-Astrocyte Axis: New Insights into the Mechanisms of Comorbid Major Depressive Disorder in Type 2 Diabetes Mellitus.Molecular neurobiology · 2026Review
- Blood ATX(N) Biomarkers and Cognitive Dysfunction in Severe Mental Illnesses.International journal of molecular sciences · 2026Review
- Suicide Behavior as a Distinct Psychobiology in Major Depression.Advances in experimental medicine and biology · 2026Review
- Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes.Antioxidants (Basel, Switzerland) · 2025Review
- Possible antidepressant mechanism of acupuncture: targeting neuroplasticity.Frontiers in neuroscience · 2025Review
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Identification of Potential Biomarkers for Major Depressive Disorder: Based on Integrated Bioinformatics and Clinical Validation.Molecular neurobiology · 2024Article
- Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives.Molecular neurobiology · 2024Review
- Reactive Astrocytosis-A Potential Contributor to Increased Suicide in Long COVID-19 Patients?Brain sciences · 2024Review
- Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review.Brain sciences · 2024Review
- Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder?Translational psychiatry · 2023Article
- Astrocytes in Post-Stroke Depression: Roles in Inflammation, Neurotransmission, and Neurotrophin Signaling.Cellular and molecular neurobiology · 2023Review
- Formulating treatment of major psychiatric disorders: algorithm targets the dominantly affected brain cell-types.Discover mental health · 2023Review
- Construction of antibiotic-induced depression mice model and the function of intestinal microbiota.Frontiers in microbiology · 2023Article
- Astrocytes as Context for the Involvement of Myelin and Nodes of Ranvier in the Pathophysiology of Depression and Stress-Related Disorders.Journal of psychiatry and brain science · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundNorepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input.
methodsThe expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs).
resultsAstrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods. LIMITATIONS: Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide.
conclusionMajor depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.