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Astrogliosis comprises a variety of changes in astrocytes that occur in a context‐specific manner, triggered by temporally diverse signaling events that vary with the nature and severity of brain insults. However, most mechanisms underlying astrogliosis were described using animals, which fail to reproduce some aspects of human astroglial signaling. Here, we report an in vitro model to study astrogliosis...
Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and pre‐myelinating OLGs, and during the process of active myelin wrapping, the forward...
Inflammation can be resolved by pro‐homeostatic lipids called specialized pro‐resolving mediators (SPMs) upon activation of their receptors. Dysfunctional inflammatory resolution is now considered as a driver of chronic neuroinflammation and Alzheimer's disease (AD) pathogenesis. We have previously shown that SPM levels were reduced and also that SPM‐binding receptors were increased in patients with...
The maintenance of progenitor states or the differentiation of progenitors into specific lineages requires epigenetic remodeling of the gene expression program. In the central nervous system, oligodendrocyte progenitors (OPCs) give rise to oligodendrocytes (OLs), whose main function has been thought to be to produce myelin, a lipid‐rich structure insulating the axons. However, recent findings suggest...
Schwann cells (SCs) are the main glial cells present in the peripheral nervous system (PNS). Their primary functions are to insulate peripheral axons to protect them from the environment and to enable fast conduction of electric signals along big caliber axons by enwrapping them in a thick myelin sheath rich in lipids. In addition, SCs have the peculiar ability to foster axonal regrowth after a lesion...
Schwann cells develop from neural crest cells in an ordered series of events and give rise to myelinating and nonmyelinating subtypes. In their mature state, myelinating Schwann cells produce myelin sheaths that provide trophic support to axons and allow saltatory conduction in the vertebrate peripheral nervous system. Each step of Schwann cell development requires defined changes in chromatin structure...
Oligodendrocytes, the myelinating cells in the vertebrate central nervous system, produce myelin sheaths to enable saltatory propagation of action potentials. The process of oligodendrocyte myelination entails a stepwise progression from precursor specification to differentiation, which is coordinated by a series of transcriptional and chromatin remodeling events. ATP‐dependent chromatin remodeling...
The nervous system consists of several hundred neuronal subtypes and glial cells that show specific gene expression and are generated from common ancestors, neural stem cells (NSCs). As the experimental techniques and molecular tools to analyze epigenetics and chromatin structures are rapidly advancing, the comprehensive events and genome‐wide states of DNA methylation, histone modifications, and...
Microglia perform multiple tasks that are essential to ensure proper cerebral functions, including synaptic remodeling, clearance of molecular debris, prevention of infections, and so forth. Furthermore, accumulating genetic and pathological evidence implicates microglial cell activity in the etiology of numerous neurodegenerative diseases and psychiatric disorders. Given this, efforts aimed at understanding...
DNA methylation is one of many epigenetic marks, which directly modifies base residues, usually cytosines, in a multiple‐step cycle. It has been linked to the regulation of gene expression and alternative splicing in several cell types, including during cell lineage specification and differentiation processes. DNA methylation changes have also been observed during aging, and aberrant methylation...
Among the myeloid cells in the central nervous system (CNS) microglia are the main representatives of the innate immune system. Microglial fulfil tasks beyond phagocytosing debris and host defense against invading microorganism. During brain development microglia guide for example neurons for proper CNS formation, in adulthood they maintain tissue homeostasis and in aging microglia may become pro‐inflammatory...
Microglia are CNS‐resident cells involved in immune surveillance and maintenance of intercellular homeostasis, while also contributing to neurologic pathologies. MicroRNAs (miRNAs) are a class of small (~22 nucleotides) single‐stranded noncoding RNAs that participate in gene regulation at the post‐transcriptional level. miRNAs typically bind to the untranslated region (3′ UTR) of RNAs. It has been...
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...
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