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Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)‐to‐Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning‐relevant processes during early postnatal development. Until now, the role of microglia in pruning remains under intense investigation...
The present study examines functional contributions of microglia in host defense, demyelination, and remyelination following infection of susceptible mice with a neurotropic coronavirus. Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse...
Dystonin (Dst) is a causative gene for Dystonia musculorum (dt) mice, which is an inherited disorder exhibiting dystonia‐like movement and ataxia with sensory degeneration. Dst is expressed in a variety of tissues, including the central nervous system and the peripheral nervous system (PNS), muscles, and skin. However, the Dst‐expressing cell type(s) for dt phenotypes have not been well characterized...
Astrocytes are fundamental for maintaining brain homeostasis and are commonly involved in the progression of neurodegenerative diseases including Alzheimer's disease (AD). In response to injury or toxic material, astrocytes undergo activation that results in hypertrophy and process ramification. Although numerous studies have shown that reactive astrocytes are intimately related to the pathogenesis...
Inflammation and metabolism are intrinsically linked with inflammatory stimuli inducing metabolic changes in cells and, in turn, metabolic capacity determining cellular inflammatory responses. Although well characterized in peripheral immune cells there is comparatively less known about these “immunometabolic” responses in astrocytes. In this study, we tested the hypothesis that the astrocytic inflammatory...
During aging humans lose midbrain dopamine neurons, but not all dopamine regions exhibit vulnerability to neurodegeneration. Microglia maintain tissue homeostasis and neuronal support, but microglia become senescent and likely lose some of their functional abilities. Since aging is the greatest risk factor for Parkinson's disease, we hypothesized that aging‐related changes in microglia and neurons...
Microglia‐mediated inflammation exerts adverse effects in ischemic stroke and in neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the voltage‐gated potassium channel Kv1.3 is required for microglia activation. Both genetic deletion and pharmacological inhibition of Kv1.3 are effective in reducing microglia activation and the associated inflammatory responses, as well as...
Despite sigma‐1 receptor (Sig‐1R) is a promising therapeutic target in depression, little is known regarding the cellular mechanisms underlying its antidepressant responses. Here, we demonstrated that astrocyte can be a direct cellular target of Sig‐1R exerting antidepressant‐like effect. In multiple behavioral models including forced swimming test (FST), tail suspension test (TST), open field test...
Focal ischemic stroke (FIS) is a leading cause of human death. Glial scar formation largely caused by reactive astrogliosis in peri‐infarct region (PIR) is the hallmark of FIS. Glial cell‐derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell‐line supernatant and is a potent survival neurotrophic factor. Here, using CreERT2–LoxP recombination technology, we generated inducible...
Microglial erythrophagocytosis is crucial in injury response to hemorrhagic stroke. We hypothesized that regulation of microglial erythrophagocytosis via HO‐1/CO depends on a pathway involving reactive oxygen species (ROS) and CD36 surface‐expression. The microglial BV‐2 cell line and primary microglia (PMG) were incubated +/−blood and +/−CO‐exposure. PMG isolated from tissue‐specific HO‐1‐deficient...
Widespread tumor cell invasion is a fundamental property of diffuse gliomas and is ultimately responsible for their poor prognosis. A greater understanding of basic mechanisms underlying glioma invasion is needed to provide insights into therapies that could potentially counteract them. While none of the currently available in vitro models can fully recapitulate the complex interactions of glioma...
Neuronal signaling in the central nervous system (CNS) associates with release of K+ into the extracellular space resulting in transient increases in [K+]o. This elevated K+ is swiftly removed, in part, via uptake by neighboring glia cells. This process occurs in parallel to the [K+]o elevation and glia cells thus act as K+ sinks during the neuronal activity, while releasing it at the termination...
Mitophagy is essential for the health of dopaminergic neurons because mitochondrial damage is a keystone of Parkinson's disease. The aim of the present work was to study the degradation of mitochondria in the degenerating dopaminergic synapse. Adult Sprague–Dawley rats and YFP‐Mito‐DAn mice with fluorescent mitochondria in dopaminergic neurons were injected in the lateral ventricles with 6‐hydroxydopamine,...
Abnormalities of the peripheral myelin protein 22 (PMP22) gene, including duplication, deletion and point mutations are a major culprit in Type 1 Charcot–Marie–Tooth (CMT) diseases. The complete absence of PMP22 alters cholesterol metabolism in Schwann cells, which likely contributes to myelination deficits. Here, we examined the subcellular trafficking of cholesterol in distinct models of PMP22‐linked...
Myelin sheaths, which insulate the axons and ensure saltatory conduction of the nerve impulse, are generated and maintained via largely uncharacterized mechanisms. Ermin is an oligodendrocyte‐specific protein associated with the cytoskeleton, but how it regulates cytoskeletal remodeling during oligodendrocyte differentiation and its role in myelin maintenance are not clear. To address this, we generated...
Since the introduction of the combined antiretroviral therapy, HIV‐1 infection has become a manageable chronic disease in which patients display a life expectancy almost identical to the general population. Nevertheless, various age‐related pathologies such as neurocognitive disorders have emerged as serious complications. A “shock and kill” strategy using latency‐reversing agents (LRA) to reactivate...
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