Implication of cerebral astrocytes in major depression: A review of fine neuroanatomical evidence in humans
- PMID: 33734498
- DOI: 10.1002/glia.23994
Implication of cerebral astrocytes in major depression: A review of fine neuroanatomical evidence in humans
Abstract
Postmortem investigations have implicated astrocytes in many neurological and psychiatric conditions. Multiple brain regions from individuals with major depressive disorder (MDD) have lower expression levels of astrocyte markers and lower densities of astrocytes labeled for these markers, suggesting a loss of astrocytes in this mental illness. This paper reviews the general properties of human astrocytes, the methods to study them, and the postmortem evidence for astrocyte pathology in MDD. When comparing astrocyte density and morphometry studies, astrocytes are more abundant and smaller in human subcortical than cortical brain regions, and immunohistochemical labeling for the astrocyte markers glial fibrillary acidic protein (GFAP) and vimentin (VIM) reveals fewer than 15% of all astrocytes that are present in cortical and subcortical regions, as revealed using other staining techniques. By combining astrocyte densities and morphometry, a model was made to illustrate that domain organization is mostly limited to GFAP-IR astrocytes. Using these markers and others, alterations of astrocyte densities appear more widespread than those for astrocyte morphologies throughout the brain of individuals having died with MDD. This review suggests how reduced astrocyte densities may relate to the association of depressive episodes in MDD with elevated S100 beta (S100B) cerebrospinal fluid serum levels. Finally, a potassium imbalance theory is proposed that integrates the reduced astrocyte densities generated from postmortem studies with a hypothesis for the antidepressant effects of ketamine generated from rodent studies.
Keywords: astrocyte; human; morphology; postmortem; stereology.
© 2021 Wiley Periodicals LLC.
Similar articles
-
Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue.Curr Drug Targets. 2013 Oct;14(11):1225-36. doi: 10.2174/13894501113149990156. Curr Drug Targets. 2013. PMID: 23469922 Free PMC article. Review.
-
Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder.Neuroscience. 2016 Mar 1;316:209-20. doi: 10.1016/j.neuroscience.2015.12.044. Epub 2015 Dec 30. Neuroscience. 2016. PMID: 26742791 Free PMC article.
-
Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides.Front Psychiatry. 2021 Feb 4;12:640963. doi: 10.3389/fpsyt.2021.640963. eCollection 2021. Front Psychiatry. 2021. PMID: 33613346 Free PMC article.
-
Characterization of Vimentin-Immunoreactive Astrocytes in the Human Brain.Front Neuroanat. 2020 Jul 30;14:31. doi: 10.3389/fnana.2020.00031. eCollection 2020. Front Neuroanat. 2020. PMID: 32848635 Free PMC article.
-
Role of Astrocytes in Major Neuropsychiatric Disorders.Neurochem Res. 2021 Oct;46(10):2715-2730. doi: 10.1007/s11064-020-03212-x. Epub 2021 Jan 7. Neurochem Res. 2021. PMID: 33411227 Review.
Cited by
-
Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis.J Neuroinflammation. 2023 Mar 6;20(1):59. doi: 10.1186/s12974-023-02713-0. J Neuroinflammation. 2023. PMID: 36879305 Free PMC article.
-
Histological Studies of the Ventricular-Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche.J Histochem Cytochem. 2021 Dec;69(12):819-834. doi: 10.1369/00221554211032003. Epub 2021 Jul 26. J Histochem Cytochem. 2021. PMID: 34310246 Free PMC article. Review.
-
Intelligent diagnosis of major depression disease based on multi-layer brain network.Front Neurosci. 2023 Mar 16;17:1126865. doi: 10.3389/fnins.2023.1126865. eCollection 2023. Front Neurosci. 2023. PMID: 37008226 Free PMC article.
-
Glutamate shall not pass: a mechanistic role for astrocytic O-GlcNAc transferase in stress and depression.J Clin Invest. 2023 Apr 3;133(7):e168662. doi: 10.1172/JCI168662. J Clin Invest. 2023. PMID: 37009895 Free PMC article.
-
Bibliometric insights into astrocytic roles in depression and treatment.Front Cell Neurosci. 2025 Jan 15;18:1521398. doi: 10.3389/fncel.2024.1521398. eCollection 2024. Front Cell Neurosci. 2025. PMID: 39882216 Free PMC article.
References
REFERENCES
-
- Akhisaroglu, M., Manev, R., Akhisaroglu, E., Uz, T., & Manev, H. (2003). Both aging and chronic fluoxetine increase S100B content in the mouse hippocampus. Neuroreport, 14(11), 1471-1473. https://doi.org/10.1097/00001756-200308060-00013
-
- Altshuler, L. L., Abulseoud, O. A., Foland-Ross, L., Bartzokis, G., Chang, S., Mintz, J., … Vinters, H. V. (2010). Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder. Bipolar Disorders, 12(5), 541-549. https://doi.org/10.1111/j.1399-5618.2010.00838.x
-
- Ambrée, O., Bergink, V., Grosse, L., Alferink, J., Drexhage, H. A., Rothermundt, M., … Birkenhäger, T. K. (2016). S100b serum levels predict treatment response in patients with melancholic depression. International Journal of Neuropsychopharmacology, 19(3), pyv103. https://doi.org/10.1093/ijnp/pyv103
-
- Ampuero, E., Luarte, A., Santibañez, M., Varas-Godoy, M., Toledo, J., Diaz-Veliz, G., … Wyneken, U. (2015). Two chronic stress models based on movement restriction in rats respond selectively to antidepressant drugs: Aldolase c as a potential biomarker. International Journal of Neuropsychopharmacology, 18(10), pyv038.
-
- Andriezen, W. L. (1893). The neuroglia elements in the human brain. British Medical Journal, 2(1700), 227-230.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous