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Browsing by Subject "Oligodendrocytes"
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Item Hedgehog Signaling in CNS Remyelination(MDPI, 2022-07-21) Fang, Minxi; Tang, Tao; Qiu, Mengsheng; Xu, Xiaofeng; Anatomy, Cell Biology and Physiology, School of MedicineRemyelination is a fundamental repair process in the central nervous system (CNS) that is triggered by demyelinating events. In demyelinating diseases, oligodendrocytes (OLs) are targeted, leading to myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination often fails in the progression of demyelinating diseases, increased understanding of the mechanisms and identification of targets that regulate myelin regeneration becomes crucial. To date, several signaling pathways have been implicated in the remyelination process, including the Hedgehog (Hh) signaling pathway. This review summarizes the current data concerning the complicated roles of the Hh signaling pathway in the context of remyelination. We will highlight the open issues that have to be clarified prior to bringing molecules targeting the Hh signaling to demyelinating therapy.Item Immunological Markers for Central Nervous System Glia(Springer, 2023) Huang, Hao; He, Wanjun; Tang, Tao; Qiu, Mengsheng; Anatomy, Cell Biology and Physiology, School of MedicineGlial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.Item O12.3.Effects of Fingolimod, A Potent Anti-Inflammatory Agent, On Brain Structure, Function, And Symptoms in Schizophrenia(Oxford University Press, 2019-04) Breier, Alan; Hummer, Tom; Vohs, Jennifer; Mehdyoun, Nicole; Liffick, Emily; Francis, Michael; Medicine, School of MedicineBackground New medications with novel targets are needed for schizophrenia. Several lines of evidence indicate that inflammatory processes including aberrant lymphocytic activity may be related to the pathophysiology of this illness. These data suggest that agents with anti-inflammatory actions, including modulation of lymphocytes and their inflammatory substrates, may prove to be efficacious for schizophrenia. Fingolimod is a powerful anti-inflammatory agent that is used in the treatment of relapsing multiple sclerosis. It is a sphingosine-1-phosphate (S1P) receptor modulator that decreases circulating lymphocytes through sequestration in lymph tissues. In addition, evidence suggest that it stimulates oligodendrocytes and may enhance white matter integrity. The purpose of this study was to assess the effects of fingolimod in schizophrenia. Methods Subjects with schizophrenia (N=40) were recruited through the Indiana University Psychotic Disorders Programs and randomized 1:1 in a double-blind, eight-week clinical trial of fingolimod 0.5 mg/day and placebo. Circulating total lymphocytes were determined and effects were assessed on symptoms (PANSS), cognition (BACS), plasma cytokines, white matter integrity (DTI) and cortical connectivity (resting fMRI). Results Results revealed a significant decrease in lymphocytes in subjects taking fingolimod versus placebo (treatment x time; F = 61.2, p < 0.001). Fingolimod treated subjects had a mean maximal drop in lymphocytes from baseline of 79.2% with all fingolimod treated subjects experiencing decrements greater than 60%. There was a trend toward higher mean skeletal fractional anisotropy (FA) post-treatment in the fingolimod group. Within the fingolmiod group, there were significant or trend-level correlations between FA increase and decrease in lymphocytes in the genu and body of the corpus collosum and the right superior longitudinal fasciculus. There were also significant group-by-visit interactions in connectivity of left prefrontal cortical (PFC) seeds with clusters in the cerebellum, driven by higher PFC-cerebellum connectivity following fingolimod treatment. There were no improvements (treatment x time) in PANSS total (F = 0.66, p= 0.52), any of the PANSS subscales, or BACS composite score (F = 0.54, p = 0.44). Serious side effects were not observed, and a full safety report will be provided. Discussion Fingolimod produced a strong anti-inflammatory response with substantial reductions in circulating lymphocytes in all treated subjects. Brain effects were observed. However, this response was not accompanied by improvements in symptoms or cognition. These data suggest that fingolimod’s target of S1P modulation and robust anti-inflammatory warrant further investigation in schizophrenia.Item Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction(MDPI, 2024-05-30) Tizabi, Yousef; Getachew, Bruk; Hauser, Sheketha R.; Tsytsarev, Vassiliy; Manhães, Alex C.; da Silva, Victor Diogenes Amaral; Psychiatry, School of MedicineMood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, the specific contributions of neurotrophic factors, neuroinflammation, and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes, and synantocytes) on phenotypic manifestation of mood disorders or SUD are emphasized. In addition, use of this knowledge in the potential development of novel therapeutics is touched upon.