Did you mean: macrogliosis
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Neuron Jan 2023In addition to tau and Aβ pathologies, inflammation plays an important role in Alzheimer's disease (AD). Variants in APOE and TREM2 increase AD risk. ApoE4 exacerbates...
In addition to tau and Aβ pathologies, inflammation plays an important role in Alzheimer's disease (AD). Variants in APOE and TREM2 increase AD risk. ApoE4 exacerbates tau-linked neurodegeneration and inflammation in P301S tau mice and removal of microglia blocks tau-dependent neurodegeneration. Microglia adopt a heterogeneous population of transcriptomic states in response to pathology, at least some of which are dependent on TREM2. Previously, we reported that knockout (KO) of TREM2 attenuated neurodegeneration in P301S mice that express mouse Apoe. Because of the possible common pathway of ApoE and TREM2 in AD, we tested whether TREM2 KO (T2KO) would block neurodegeneration in P301S Tau mice expressing ApoE4 (TE4), similar to that observed with microglial depletion. Surprisingly, we observed exacerbated neurodegeneration and tau pathology in TE4-T2KO versus TE4 mice, despite decreased TREM2-dependent microgliosis. Our results suggest that tau pathology-dependent microgliosis, that is, TREM2-independent microgliosis, facilitates tau-mediated neurodegeneration in the presence of ApoE4.
Topics: Mice; Animals; Apolipoprotein E4; Alzheimer Disease; Inflammation; Microglia; Disease Models, Animal; Membrane Glycoproteins; Receptors, Immunologic
PubMed: 36368315
DOI: 10.1016/j.neuron.2022.10.022 -
Proceedings of the National Academy of... Feb 2023Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). Upon pathological...
Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). Upon pathological stimulation, microglia are converted from a surveillant to an overactivated phenotype. However, the molecular characters of proliferating microglia and their contributions to the pathogenesis of neurodegeneration remain unclear. Here, we identify chondroitin sulfate proteoglycan 4 ( also known as neural/glial antigen 2)-expressing microglia as a specific subset of microglia with proliferative capability during neurodegeneration. We found that the percentage of microglia was increased in mouse models of PD. The transcriptomic analysis of microglia revealed that the subcluster microglia displayed a unique transcriptomic signature, which was characterized by the enrichment of orthologous cell cycle genes and a lower expression of genes responsible for neuroinflammation and phagocytosis. Their gene signatures were also distinct from that of known disease-associated microglia. The proliferation of quiescent microglia was evoked by pathological α-synuclein. Following the transplantation in the adult brain with the depletion of endogenous microglia, microglia grafts showed higher survival rates than their counterparts. Consistently, microglia were detected in the brain of AD patients and displayed the expansion in animal models of AD. These findings suggest that microglia are one of the origins of microgliosis during neurodegeneration and may open up a avenue for the treatment of neurodegenerative diseases.
Topics: Mice; Animals; Microglia; Parkinson Disease; Alzheimer Disease; Neurodegenerative Diseases; Phagocytosis
PubMed: 36795751
DOI: 10.1073/pnas.2210643120 -
Progress in Neurobiology Apr 1999Damage to the central nervous system (CNS) elicits the activation of both astrocytes and microglia. This review is focused on the principal features that characterize... (Review)
Review
Damage to the central nervous system (CNS) elicits the activation of both astrocytes and microglia. This review is focused on the principal features that characterize the activation of microglia after CNS injury. It provides a critical discussion of concepts regarding microglial biology that include the relationship between microglia and macrophages, as well as the role of microglia as immunocompetent cells of the CNS. Mechanistic and functional aspects of microgliosis are discussed primarily in the context of microglial neuronal interactions. The controversial issue of whether reactive microgliosis is a beneficial or a harmful process is addressed, and a resolution of this dilemma is offered by suggesting different interpretations of the term 'activated microglia' depending on its usage during in vivo or in vitro experimentation.
Topics: Animals; Cell Communication; Gliosis; Humans; Immunocompetence; Microglia; Neurons
PubMed: 10221782
DOI: 10.1016/s0301-0082(98)00069-0 -
The Neuroscientist : a Review Journal... Apr 2016Microgliosis is an intense reaction of CNS microglia to pathogenic insults. One of the characteristic features of microgliosis is an increase in the number of activated... (Review)
Review
Microgliosis is an intense reaction of CNS microglia to pathogenic insults. One of the characteristic features of microgliosis is an increase in the number of activated microglia at the site of lesion. Ontogenically, microglia are considered to be of mesodermal lineage in the adult CNS, but the origin of the accumulated microglia in pathological conditions remains controversial. Some studies indicate that circulating cells from the bloodstream can infiltrate the CNS and contribute to microglial pool, but some studies suggest that local expansion of reactive microglia is the sole source for parenchymal microglia. Recent data suggest that latent progenitors may also exist in the CNS. Available evidence suggests that multiple sources of microglia may exist under various neurological conditions. In this review, we compare the prevalent views and supporting evidence from different experimental models and provide an overview on the origins of microgliosis.
Topics: Animals; Brain; Brain Injuries; Cell Proliferation; Gliosis; Humans; Microglia
PubMed: 25672621
DOI: 10.1177/1073858415572079 -
Neurochemistry International May 2021Microglial cells are the resident immune cells of the central nervous system. They are essential for normal functioning, maintenance of tissue integrity, clearance of... (Review)
Review
Microglial cells are the resident immune cells of the central nervous system. They are essential for normal functioning, maintenance of tissue integrity, clearance of dying neurons, elimination of pathogens, development and maintenance of homeostasis of the CNS. Many studies have consistently reported that oxidative stress and associated neuroinflammation mediated by microglial cells have a degenerating effect on dopaminergic neurons. In Parkinson's disease, the microglial cells by a process called microgliosis undergo rapid proliferation, accumulate at the site of tissue injury and undergo phenotypic and functional changes that result in the release of massive amounts of free radicals causing inflammation and neurodegeneration of dopaminergic neurons. Following the discovery of the irrefutable role oxidative stress and associated neuroinflammation, several proven antioxidants were tested for possible protective and therapeutic potential in Parkinson's disease but the results so far have not been encouraging and equivocal. Consequently, it is rational to look for endogenous targets that enhance the oxidative defense mechanism against free radicals and protect dopaminergic neurons from neuroinflammation and neurodegeneration. One such target is a nuclear factor-erythroid -2-related factor 2 (Nrf2). Nrf2 is a redox-sensitive transcription factor located in the cytoplasm of the cells that helps cells adapt to oxidative stress and inflammation by upregulating the expression of almost 200 cytoprotective genes. Fractalkine exists in a transmembrane form and a soluble form and is a cytokine that links microglial cells and Nrf2. The fractalkine receptors, expressed exclusively by microglial cells, on activation by fractalkine protects dopaminergic neurons from degeneration caused by free radicals and pro-inflammatory mediators through increased expression of Nrf2 dependent genes. The current anti Parkinsonism drugs do not cure the disease and also cause several debilitating motor and non-motor adverse drug effects. So it becomes imperative to explore novel targets and discover novel therapeutic agents to treat Parkinson's disease in a better way and improve the quality of life of patients with Parkinson's disease.
Topics: Animals; Antiparkinson Agents; Dopaminergic Neurons; Gliosis; Humans; Inflammation Mediators; Microglia; NF-E2-Related Factor 2; Oxidative Stress; Parkinson Disease
PubMed: 33689805
DOI: 10.1016/j.neuint.2021.105014 -
Osteoarthritis and Cartilage May 2017
Review
Topics: Central Nervous System Sensitization; Humans; Inflammation; Microglia; Osteoarthritis; Pain; Pain Management
PubMed: 28223124
DOI: 10.1016/j.joca.2017.02.798 -
Trends in Neurosciences Dec 2022Traditionally, lymphocytic interferon γ (IFN-γ) was considered to be a simple 'booster' of proinflammatory responses by microglia (brain-resident macrophages) during... (Review)
Review
Traditionally, lymphocytic interferon γ (IFN-γ) was considered to be a simple 'booster' of proinflammatory responses by microglia (brain-resident macrophages) during bacterial or viral infection. Recent slice culture (in situ) and in vivo studies suggest, however, that IFN-γ has a unique role in microglial activation. Priming by IFN-γ results in proliferation (microgliosis), enhanced synapse elimination, and moderate nitric oxide release sufficient to impair synaptic transmission, gamma rhythm activity, and cognitive functions. Moreover, IFN-γ is pivotal for driving Toll-like receptor (TLR)-activated microglia into neurotoxic phenotypes that induce energetic and oxidative stress, severe network dysfunction, and neuronal death. Pharmacological targeting of activated microglia could be beneficial during elevated IFN-γ levels, blood-brain barrier leakage, and parenchymal T lymphocyte infiltration associated with, for instance, encephalitis, multiple sclerosis, and Alzheimer's disease.
Topics: Microglia; Interferon-gamma; Cytokines; Nitric Oxide; Neural Networks, Computer
PubMed: 36283867
DOI: 10.1016/j.tins.2022.10.007 -
Neuron Dec 2018The previous decade has seen a rapid increase in microglial studies on pain, with a unique focus on microgliosis in the spinal cord after nerve injury and neuropathic... (Review)
Review
The previous decade has seen a rapid increase in microglial studies on pain, with a unique focus on microgliosis in the spinal cord after nerve injury and neuropathic pain. Numerous signaling molecules are altered in microglia and contribute to the pathogenesis of pain. Here, we discuss how microglial signaling regulates spinal cord synaptic plasticity in acute and chronic pain conditions with different degrees and variations of microgliosis. We highlight that microglial mediators such as pro- and anti-inflammatory cytokines are powerful neuromodulators that regulate synaptic transmission and pain via neuron-glial interactions. We also reveal an emerging role of microglia in the resolution of pain, in part via specialized pro-resolving mediators including resolvins, protectins, and maresins. We also discuss a possible role of microglia in chronic itch.
Topics: Animals; Central Nervous System; Cytokines; Humans; Inflammation; Microglia; Pain; Pain Management; Signal Transduction; Up-Regulation
PubMed: 30571942
DOI: 10.1016/j.neuron.2018.11.009 -
Cell Reports Mar 2023Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood....
Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.
Topics: Humans; Animals; Mice; COVID-19; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Toll-Like Receptor 4; Post-Acute COVID-19 Syndrome; Cognitive Dysfunction
PubMed: 36857178
DOI: 10.1016/j.celrep.2023.112189 -
Current Neuropharmacology 2021Neurological disorders (ND) are the central nervous system (CNS) related complications originated by enhanced oxidative stress, mitochondrial failure and overexpression... (Review)
Review
Neurological disorders (ND) are the central nervous system (CNS) related complications originated by enhanced oxidative stress, mitochondrial failure and overexpression of proteins like S100B. S100B is a helix-loop-helix protein with the calcium-binding domain associated with various neurological disorders through activation of the MAPK pathway, increased NF-kB expression resulting in cell survival, proliferation and gene up-regulation. S100B protein plays a crucial role in Alzheimer's disease, Parkinson's disease, multiple sclerosis, Schizophrenia and epilepsy because the high expression of this protein directly targets astrocytes and promotes neuroinflammation. Under stressful conditions, S100B produces toxic effects mediated through receptor for advanced glycation end products (AGE) binding. S100B also mediates neuroprotection, minimizes microgliosis and reduces the expression of tumor necrosis factor (TNF-alpha) but that are concentration- dependent mechanisms. Increased level of S100B is useful for assessing the release of inflammatory markers, nitric oxide and excitotoxicity dependent neuronal loss. The present review summarizes the role of S100B in various neurological disorders and potential therapeutic measures to reduce the prevalence of neurological disorders.
Topics: Astrocytes; Biomarkers; Humans; Nervous System Diseases; Parkinson Disease; S100 Calcium Binding Protein beta Subunit
PubMed: 32727332
DOI: 10.2174/1570159X18666200729100427