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Bmal1 is an essential component of the molecular clockwork, which drives circadian rhythms in cell function. In Bmal1‐deficient (Bmal1−/−) mice, chronodisruption is associated with cognitive deficits and progressive brain pathology including astrocytosis indicated by increased expression of glial fibrillary acidic protein (GFAP). However, relatively little is known about the impact of Bmal1‐deficiency...
Impaired myelination is a key feature in neonatal hypoxia/ischemia (HI), the most common perinatal/neonatal cause of death and permanent disabilities, which is triggered by the establishment of an inflammatory and hypoxic environment during the most critical period of myelin development. This process is dependent on oligodendrocyte precursor cells (OPCs) and their capability to differentiate into...
Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating...
The glycoproteins and glycolipids of the cell surface have sugar chains that normally terminate in a sialic acid residue, but inflammatory activation of myeloid cells can cause sialidase enzymes to remove these residues, resulting in desialylation and altered activity of surface receptors, such as the phagocytic complement receptor 3 (CR3). We found that activation of microglia with lipopolysaccharide...
The high‐mobility‐group (HMG)‐domain protein Sox9 is one of few transcription factors implicated in gliogenesis in the vertebrate central nervous system. To further study the role of Sox9 in early spinal cord development, we generated a mouse that allows expression of Sox9 in a temporally and spatially controlled manner. Using this mouse, we show that premature Sox9 expression in neural precursor...
Microglia constantly survey the brain microenvironment and rapidly adopt different phenotypes in response to environmental stimuli. Such dynamic functions require a unique metabolism and bioenergetics. However, little is known about the basic metabolism of microglia and how metabolic changes regulate microglia function. Here, we uncover that microglia activation is accompanied by extensive transcriptional...
Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non‐cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72‐mediated ALS. Here, we use a human iPSC‐based...
Traumatic brain injury (TBI) is a major health problem with high rates of mortality and morbidity worldwide. The response of the brain to TBI is orchestrated by a number of cytokines, including interleukin‐6 (IL‐6). IL‐6 is a major cytokine in the central nervous system and it is produced by different cells, such as neurons, glial cells, and endothelial cells. Since glial cells are one of the most...
Glial fibrillary acidic protein (GFAP), a type III intermediate filament, is a marker of mature astrocytes. The expression of GFAP gene is regulated by many transcription factors (TFs), mainly Janus kinase‐2/signal transducer and activator of transcription 3 cascade and nuclear factor κ‐light‐chain‐enhancer of activated B cell signaling. GFAP expression is also modulated by protein kinase and other...
Tonic extrasynaptic GABAA receptor (GABAAR) activation is under the tight control of tonic GABA release from astrocytes to maintain the brain's excitation/inhibition (E/I) balance; any slight E/I balance disturbance can cause serious pathological conditions including epileptic seizures. However, the pathophysiological role of tonic GABA release from astrocytes has not been tested in epileptic seizures...
The role of astrocytes in the progression of Alzheimer's disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP‐TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased...
Although diabetic mice have been studied for decades, little is known about the cell type specific contributions to diabetic neuropathy (DN). Schwann cells (SCs) myelinate and provide trophic support to peripheral nervous system axons. Altered SC metabolism leads to myelin defects, which can be seen both in inherited and DNs. How SC metabolism is altered in DN is not fully understood, but it is clear...
The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double‐immunohistochemical staining for platelet‐derived growth factor receptor α (PDGFRα)...
Astrocytes form large networks, in which individual cells are connected via gap junctions. It is thought that this astroglial gap junction coupling contributes to the buffering of extracellular K+ increases. However, it is largely unknown how the control of extracellular K+ by astroglial gap junction coupling depends on the underlying activity patterns and on the magnitude of extracellular K+ increases...
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