Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis

Abstract

Complex roles for astrocytes in health and disease continue to emerge, highlighting this class of cells as integral to function and dysfunction of the nervous system. In particular, escalating evidence strongly implicates a range of changes in astrocyte structure and function associated with neuropsychiatric diseases including major depressive disorder, schizophrenia, and addiction. These changes can range from astrocytopathy, degeneration, and loss of function, to astrogliosis and hypertrophy, and can be either adaptive or maladaptive. Evidence from the literature indicates a myriad of changes observed in astrocytes from both human postmortem studies as well as preclinical animal models, including changes in expression of glial fibrillary protein, as well as changes in astrocyte morphology and astrocyte-mediated regulation of synaptic function. In this review, we seek to provide a comprehensive assessment of these findings and consequently evidence for common themes regarding adaptations in astrocytes associated with neuropsychiatric disease. While results are mixed across conditions and models, general findings indicate decreased astrocyte cellular features and gene expression in depression, chronic stress and anxiety, but increased inflammation in schizophrenia. Changes also vary widely in response to different drugs of abuse, with evidence reflective of features of astrocytopathy to astrogliosis, varying across drug classes, route of administration and length of withdrawal.

The S100B story: from biomarker to active factor in neural injury

“…). Although dysfunction of the mucosal immune system undoubtedly plays a role in the pathogenesis of inflammatory bowel disease (Kim and Cheon ), a role for the enteric nervous system (Goyal and Hirano ), located within the wall of the gastrointestinal tract, has been recognized in intestinal inflammation, also involving interactions with the intestinal microbiota (Margolis and Gershon ). Notably, enteric glial‐derived S100B has been shown to be over‐expressed, to correlate with the gut's inflammatory status and to stimulate NO production in human ulcerative colitis (Esposito et al .…”

“…; Kim et al . ; Chitnis and Weiner ; Labzin et al . ; Fehily and Fitzgerald ; Mizuma and Yenari ; Neal and Richardson ; Franklin et al .…”

Astrocytic hypertrophy in the rat ventral tegmental area following chronic morphine differs with age

“…That would clarify if reported difference in baseline labeling is methodological or inherent to the developmental nature of the immature brain. Other studies so far have only implicated pathophysiology in altered levels of GFAP labeling [50]. …”

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

“…Glial cells play a critical functional rile in brain function. Altered glial functions are known involved in the pathophysiological process in many neuropsychiatric diseases including schizophrenia . Previous work on miRNA in schizophrenia is focused on neuronal functions, how the glial miRNA contributes to the pathogenesis and development is largely unknown.…”