Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities

Mata-Martínez, Esperanza; Dı́az-Muñoz, Mauricio; Vázquez‐Cuevas, Francisco G.

doi:10.3389/fncel.2022.929529

Cited by 12 publications

(3 citation statements)

References 150 publications

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“…Early studies suggested that the NLRP3 inflammasome is only expressed in the central nervous system microglia and has a role in regulating neuroinflammation. Current studies have shown that astrocytes can assemble different inflammasomes and participate in various neurological diseases [ 38 , 39 ]. In the present study, we further analyzed the changes of astrocytes before and after NLRP3 inhibition in the CIH model, finding that inhibition of NLRP3 could alleviate CIH-induced astrocyte activation and increase the expression of A2-type astrocytes.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia

et al. 2022

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Background Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear. Methods We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1β. Results The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1β) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1β pathway-related proteins decreased. Conclusion The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH

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Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia

et al. 2022

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“…Aβ stimulates the NLRP3 inflammasome, a cytoplasmic tricomplex made up of the effector protein caspase-1, an adapter protein called ASC, and a sensor protein called NLRP3, which together promote IL-1β release and cause neurodegeneration [ 16 , 130 ]. ASC released by active microglia further aids in plaque formation by causing Aβ to oligomerize and aggregate, and NLRP3 inflammasome stimulation can change the microglial phagocytosis function and increase Aβ accumulation [ 131 , 132 ]. Collectively, Aβ may trigger a number of neurotoxic and inflammatory signalling in microglia that can contribute to AD pathogenesis.…”

Section: Microglia In Admentioning

confidence: 99%

Microglia and Alzheimer’s Disease

Merighi¹,

Nigro²,

Travagli³

et al. 2022

IJMS

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There is a huge need for novel therapeutic and preventative approaches to Alzheimer’s disease (AD) and neuroinflammation seems to be one of the most fascinating solutions. The primary cell type that performs immunosurveillance and helps clear out unwanted chemicals from the brain is the microglia. Microglia work to reestablish efficiency and stop further degeneration in the early stages of AD but mainly fail in the illness’s later phases. This may be caused by a number of reasons, e.g., a protracted exposure to cytokines that induce inflammation and an inappropriate accumulation of amyloid beta (Aβ) peptide. Extracellular amyloid and/or intraneuronal phosphorylated tau in AD can both activate microglia. The activation of TLRs and scavenger receptors, inducing the activation of numerous inflammatory pathways, including the NF-kB, JAK-STAT, and NLRP3 inflammasome, facilitates microglial phagocytosis and activation in response to these mediators. Aβ/tau are taken up by microglia, and their removal from the extracellular space can also have protective effects, but if the illness worsens, an environment that is constantly inflamed and overexposed to an oxidative environment might encourage continuous microglial activation, which can lead to neuroinflammation, oxidative stress, iron overload, and neurotoxicity. The complexity and diversity of the roles that microglia play in health and disease necessitate the urgent development of new biomarkers that identify the activity of different microglia. It is imperative to comprehend the intricate mechanisms that result in microglial impairment to develop new immunomodulating therapies that primarily attempt to recover the physiological role of microglia, allowing them to carry out their core function of brain protection.

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“…In addition to neurons, glial cells are fundamental for CNS proper functioning (Nampoothiri et al, 2022 ), as well as in neural pathologies (Mata-Martínez et al, 2022 ). Miranda-Negrón and García-Arrarás review how radial glia and radial glia-like cells participate in neurogenesis and regeneration during homeostasis and in response to injury, using the echinoderm Holothuria glaberrima .…”

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confidence: 99%