Glial Purinergic Signals and Psychiatric Disorders

Emotion-related neural networks are regulated in part by the activity of glial cells, and glial dysfunction can be directly related to emotional diseases such as depression. Here, we discuss three different therapeutic strategies involving astrocytes that are effective for treating depression. First, the antidepressant, fluoxetine, acts on astrocytes and increases exocytosis of ATP. This has therapeutic effects via brain-derived neurotrophic factor-dependent mechanisms. Second, electroconvulsive therapy is a well-known treatment for drug-resistant depression. Electroconvulsive therapy releases ATP from astrocytes to induce leukemia inhibitory factors and fibroblast growth factor 2, which leads to antidepressive actions. Finally, sleep deprivation therapy is well-known to cause antidepressive effects. Sleep deprivation also increases release of ATP, whose metabolite, adenosine, has antidepressive effects. These independent treatments share the same mechanism, i.e., ATP release from astrocytes, indicating an essential role of glial purinergic signals in the pathogenesis of depression.

Dichotomy in Growth and Invasion From Low to High Grade Glioma Cellular Variants

Glial dysfunction outraging CNS plasticity and integrity results into one of the most dangerous cancer, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not definitely related so far. Present study is aimed to find a relationship between this featured quadrangle from lower to higher grades of post-operative glioma tissues and their invading subsets. Elevated Ki67 associated proliferation in lower grades was supported with VEGF dependent angiogenic maintenance which found decrease unlikely in higher grades. In contrast, MMP-2 and 9 associated invasions augmented high in higher grades with dominant presence of CD204+ M2 polarized macrophages and a general increase in global DNMT1 associated methylation. Marked differences found in ECM invading cellular subsets of higher grades showing high proliferative capacity indicating rationally for recurrence, contrasting the nature of gross tumor tissue of same grade. Thus in lower grades the neoplastic lesion is more inclined for its growth while in higher grade more disposed towards tissue wreckage in support with cellular environmental milieu whereas the cellular variants and subsets of invaded cells showed different trends. Therefore, some operational dichotomy or coupling among cellular variants in glioma is active in determining its low to high grade transition and aggressive progression.

Hypothalamic Myo-Inositol and Glucose concentrations, mood symptoms and fatigue in depression: a 3 Tesla chemical-shift-imaging in vivo proton magnetic resonance spectroscopy study

Background: Many studies have confirmed altered brain Myo-Inositol (mIns) and Glucose (Glc) concentrations in depression. Alterations in the mIns-concentrations may represent a glial dysfunction and are associated mostly with depression symptoms. In comparison, alterations in the Glc-concentrations could represent impaired glucose metabolism. Despite this information, studies that assess these metabolites in the hypothalamus are missing. Therefore, this study aims to investigate mIns- and Glc-concentrations in the hypothalamus of participants with depression concerning mood symptoms and fatigue.Methods: We performed an in vivo proton magnetic resonance spectroscopy – chemical shift imaging of the hypothalamus in 49 participants (25 with depression diagnosis or DE, 24 healthy controls or HC), evaluating mIns- and Glc-concentrations. Concerning information about symptoms, we recollected information on depression symptomatology (BDI-FSTOT) and fatigue (FIS-D). For statistical analysis, we run generalized linear models by using the Poisson regression model with count data.Results: The results showed reduced hypothalamic mIns-concentration for every DE participant with higher FIS-D and higher BDI-FSTOT values (OR = 0.022; p < 0.001; CI95 [0.004 to 0.09]). Besides, the results showed increased hypothalamic Glc-concentration for every participant of the DE group and with higher BDI-FSTOT values (OR = 4.827; p = 0.002; CI95 [1.826 to 13.749]).Conclusions: These results provide initial evidence of a glial dysfunction and impaired glucose metabolism in the hypothalamus associated with mood symptoms and fatigue. Future studies are needed to confirm these pathophysiologic mechanisms.

Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome

Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder typically affecting females, resulting in a range of symptoms including autistic features, intellectual impairment, motor deterioration, and autonomic abnormalities. RTT is primarily caused by the genetic mutation of the Mecp2 gene. Initially considered a neuronal disease, recent research shows that glial dysfunction contributes to the RTT disease phenotype. In the following manuscript, we review the evidence regarding glial dysfunction and its effects on disease etiology.