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Finding causative genetic mutations is important in the diagnosis and treatment of hereditary peripheral neuropathies. This study was conducted to find new genes involved in the pathophysiology of hereditary peripheral neuropathy. We identified a new mutation in the EBP50 gene, which is co‐segregated with neuropathic phenotypes, including motor and sensory deficit in a family with Charcot–Marie–Tooth...
Microglia are a specialized population of tissue macrophages in the mammalian brain. Microglial phenotype is tightly regulated by local environmental factors, although little is known about these factors and their region‐preferred roles in regulating local neuroinflammatory responses. We hypothesized that microglia in different brain regions respond differently to neuroinflammatory stimulation and...
AMP‐activated protein kinase (AMPK) is an important energy sensor located in cells throughout the human body. From the periphery, AMPK is known to be a metabolic master switch controlling the use of energy fuels. The energy sensor is activated when the energy status of the cell is low, initiating energy‐producing pathways and deactivating energy‐consuming pathways. All brain cells are crucially dependent...
Myeloid cells such as resident retinal microglia (MG) or infiltrating blood‐derived macrophages (Mϕ) accumulate in areas of retinal ischemia and neovascularization (RNV) and modulate neovascular eye disease. Their temporospatial distribution and biological function in this process, however, remain unclarified. Using state‐of‐the‐art methods, including cell‐specific reporter mice and high‐throughput...
In vertebrates, fast saltatory conduction along myelinated axons relies on the node of Ranvier. How nodes assemble on CNS neurons is not yet fully understood. We previously described that node‐like clusters can form prior to myelin deposition in hippocampal GABAergic neurons and are associated with increased conduction velocity. Here, we used a live imaging approach to characterize the intrinsic mechanisms...
White matter (WM) pathology is a clinically predictive feature of vascular cognitive impairment and dementia (VCID). Mice overexpressing transforming growth factor‐β1 (TGF) with an underlying cerebrovascular pathology when fed a high cholesterol diet (HCD) develop cognitive deficits (VCID mice) that we recently found could be prevented by physical exercise (EX). Here, we further investigated cognitive...
As oligodendrocyte precursor cells (OPCs) are vulnerable to ischemia, their differentiation to oligodendrocytes (OLG) is impaired in chronic cerebral hypoperfusion. Astrocyte–OLG interaction is important for white matter homeostasis. Recently, reactive astrocytes were separated into two types, A1 (cytotoxic) and A2 (neurotrophic). However, their role in prolonged cerebral hypoperfusion remains unclear...
Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth‐promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation...
Aging is a major risk factor for the development of neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases are characterized by abnormal and prominent protein aggregation in the brain, partially due to deficiency in protein clearance. It has been proposed that alterations in microglia phagocytosis and debris clearance hasten the onset of neurodegeneration. Dystrophic...
During axonal ensheathment, noncompact myelin channels formed at lateral edges of the myelinating process become arranged into tight paranodal spirals that resemble loops when cut in cross section. These adhere to the axon, concentrating voltage‐dependent sodium channels at nodes of Ranvier and patterning the surrounding axon into distinct molecular domains. The signals responsible for forming and...
Epilepsy is characterized by unpredictable recurrent seizures resulting from hypersynchronous discharges from neuron assemblies. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability. Purinergic signaling is central in neuron–glia and glia–glia interactions and dysfunctions in communication pathways involving purinergic...
Astrocytes are involved in several aspects of neuronal development and properties which are altered in intellectual disability (ID). Oligophrenin‐1 is a RhoGAP protein implicated in actin cytoskeleton regulation, and whose mutations are associated with X‐linked ID. Oligophrenin‐1 is expressed in neurons, where its functions have been widely reported at the synapse, as well as in glial cells. However,...
Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several...
Mitochondrial fission mediated by cytosolic dynamin related protein 1 (Drp1) is essential for mitochondrial quality control but may contribute to apoptosis as well. Blockade of Drp1 with mitochondrial division inhibitor 1 (mdivi‐1) provides neuroprotection in several models of neurodegeneration and cerebral ischemia and has emerged as a promising therapeutic drug. In oligodendrocytes, overactivation...
Neurodegeneration is associated with inflammation and mismanaged iron homeostasis, leading to increased concentration of non‐transferrin‐bound iron (NTBI) in the brain. NTBI can be taken up by cells expressing Zrt‐, Irt‐like protein‐14 (ZIP14), which is regulated by iron overload and pro‐inflammatory cytokines, for example, interleukin‐1β (IL‐1β) and IL‐6. Here, we focus on the astrocytic involvement...
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