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.

Fluoxetine inhibited the activation of A1 reactive astrocyte in a mouse model of major depressive disorder through astrocytic 5-HT2BR/β-arrestin2 pathway

“…In many NDDs, A1 astrocytes not only have potently neurotoxic effects, but they also amplify inflammatory microglial responses [ 14 , 17 , 56 ]. Several postmortem studies found that reduced astrocyte densities may be related to depressive episodes, and elevated astrocyte protein S100 beta in cerebrospinal fluid serum could be a biomarker of MDD [ 57 ]. Recently studies implied that appearance of A1 astrocytes is associated with depression-like behaviors induced by LPS and acute stress [ 20 , 58 ].…”

Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

“…In longitudinal studies MDD patients with higher baseline S100B levels exhibit a better response to antidepressant treatment. An elevated S100B level is detected not only in psychiatric conditions but also in many other neurological disorders such as traumatic brain injury, malignant melanoma, amyotrophic lateral sclerosis, and subarachnoid hemorrhage 17 , 30 .…”

“…According to our knowledge, this is the first prospective study that tries to explore the correlation between S100B serum levels and mood disorders in adolescents and young patients. Based on the findings on glial pathology in mood disorders in adult patients 17 , 18 in our study, we provided some research questions following our hypothesis: (1) there are any differences in baseline serum S100B levels between depressed, hypomanic patients and healthy controls (2) could baseline S100B levels be influenced by clinical factors (severity of depressive and manic symptoms, medication status, family history of psychiatric and affective disorders, or gender) (3) is there a change between baseline S100B concentrations and euthymic state (as well as in a 2-year follow-up) and finally (4) do different baseline S100B levels predict diagnosis change from unipolar to bipolar disorder in young patients.…”

Histological Studies of the Ventricular–Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche

“…48 Similarly, the intermediate filament protein vimentin distinguishes stem cells in the developing and mature human and mouse V-SVZ, but can be expressed by other cell types outside the brain as well as parenchymal astrocytes. 61 Expression of the intermediate filament protein glial fibrillary acidic protein (GFAP) and the glutamate-aspartate transporter (GLAST) is also characteristic of V-SVZ stem cells, 38,62 reflective of their astrocyte-like properties. Within the V-SVZ, GFAP or GLAST expression distinguishes B-cells from their transit-amplifying and neuroblast progeny.…”