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The glymphatic system, a recently discovered macroscopic waste removal system in the brain, has many unknown aspects, especially its driving forces and relationship with sleep, and thus further explorations of the relationship between the glymphatic system and a variety of possible related diseases are urgently needed. Here, we focus on the progress in current research on the role of the glymphatic system in several common central nervous system diseases and mood disorders, discuss the structural and functional abnormalities of the glymphatic system which may occur before or during the pathophysiological progress and the possible underlying mechanisms. We emphasize the relationship between sleep and the glymphatic system under pathological conditions and summarize the common imaging techniques for the glymphatic system currently available. The perfection of the glymphatic system hypothesis and the exploration of the effects of aging and endocrine factors on the central and peripheral regulatory pathways through the glymphatic system still require exploration in the future. [ABSTRACT FROM AUTHOR]

Several trace metals, including iron, copper, manganese and zinc are essential for normal function of the nervous system. Both deficiency and excessive accumulation of these metals trigger neuropathological developments. The central nervous system (CNS) is in possession of dedicated homeostatic system that removes, accumulates, stores and releases these metals to fulfil nervous tissue demand. This system is mainly associated with astrocytes that act as dynamic reservoirs for trace metals, these being a part of a global system of CNS ionostasis. Here we overview physiological and pathophysiological aspects of astrocyte-cantered trace metals regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic loss of sleep damages health and disturbs the quality of life. Long-lasting sleep deprivation (SD) as well as sleep abnormalities are substantial risk factors for major depressive disorder, although the underlying mechanisms are not clear. Here, we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP, which activates astroglial P2X7 receptors (P2X7Rs). Activated P2X7Rs, in turn, selectively down-regulated the expression of 5-HT2B receptors (5-HT2BRs) in astrocytes. Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3a in astrocytes, but not in neurons. The over-expression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs. Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2. This latter cascade promoted the release of arachidonic acid and prostaglandin E2. The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice. Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders. [ABSTRACT FROM AUTHOR]

Introduction: Astroglia represent the main cellular homeostatic system of the central nervous system (CNS). Astrocytes are intimately involved in regulation and maintenance of neurotransmission by regulating neurotransmitters removal and turnover and by supplying neurons with neurotransmitters precursors. Astroglial cells are fundamental elements of monoaminergic transmission in the brain and in the spinal cord. Astrocytes receive monoaminergic inputs and control catabolism of monoamines through dedicated transporters and intracellular enzymatic pathways. Areas covered: Astroglial cells express serotonergic receptors; in this review, we provide an in-depth characterization of 5-HT2B receptors. Activation of these receptors triggers numerous intracellular signaling cascades that regulate expression of multiple genes. Astroglial 5-HT2B receptors are activated by serotonin-specific reuptake inhibitors, such as major anti-depressant fluoxetine. Expression of astroglial serotonin receptors undergoes remarkable changes in depression disorders, and these changes can be corrected by chronic treatment with anti-depressant drugs. Expert commentary: Depressive behaviors, which occur in rodents following chronic stress or in neurotoxic models of Parkinson disease, are associated with significant changes in the expression of astroglial, but not neuronal 5-HT2B receptors; while therapy with anti-depressants normalizes both receptors expression and depressive behavioral phenotype. In summary, astroglial serotonin receptors are linked to mood disorders and may represent a novel target for cell- and molecule-specific therapies of depression and mood disorders. [ABSTRACT FROM AUTHOR]

Abstract: Intense glucose-based energy metabolism and glutamate synthesis by astrocytes require malate–aspartate-shuttle (MAS) activity to regenerate NAD+ from NADH formed during glycolysis, since brain lacks significant glycerophosphate shuttle activity. Aralar is a necessary aspartate/glutamate exchanger for MAS function in brain. Based on cytochemical immunoassays the absence of aralar in adult astrocytes was repeatedly reported. This would mean that adult astrocytes must regenerate NAD+ by producing lactate from pyruvate, eliminating its use by oxidative and biosynthetic pathways. We alternatively used astrocytes and neurons from adult brain, freshly isolated by fluorescence-activated cell sorting, to determine aralar protein by a specific antibody and its mRNA by real-time PCR. Both protein and mRNA expressions were identical in adult neurons and astrocytes and similar to whole brain levels. The same level of aralar expression was reached in well-differentiated astrocyte cultures, but not until late development, coinciding with the late-maturing brain capability for glutamate formation and degradation. [Copyright &y& Elsevier]