Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology

Filipi, Tereza; Matusova, Zuzana; Abaffy, Pavel; Vanatko, Ondrej; Tureckova, Jana; Benesova, Sarka; Kubiskova, Monika; Kirdajová, Denisa; Zahumensky, Jakub; Valihrach, Lukás; Andĕrová, Miroslava

doi:10.1038/s41598-023-33608-y

Cited by 2 publications

(1 citation statement)

References 76 publications

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“…For example, one of the most frequent mutations in ALS is in Cu/Zn Superoxide dismutase 1 (SOD1) and rodents carrying the SOD1 (G93A) mutation is a commonly used model of this disease. In addition to other problems, including a decrease in the copy number of the mutation in chromosome 21 affecting ALS severity ( Bonifacino et al, 2021 ), a recent study showed minimal disease-related changes in microglia and oligodendrocytes in SOD1 (G93A) mouse cortex during the end-stage of ALS, which contrasts with findings in patients ( Filipi et al, 2023 ).…”

Section: Long-term Impact Of Traumatic Brain Injurymentioning

confidence: 95%

Reactive gliosis in traumatic brain injury: a comprehensive review

Amlerova,

Chmelova,

Anderova

et al. 2024

Front. Cell. Neurosci.

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Traumatic brain injury (TBI) is one of the most common pathological conditions impacting the central nervous system (CNS). A neurological deficit associated with TBI results from a complex of pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or the development of edema. The critical components contributing to CNS response, damage control, and regeneration after TBI are glial cells–in reaction to tissue damage, their activation, hypertrophy, and proliferation occur, followed by the formation of a glial scar. The glial scar creates a barrier in damaged tissue and helps protect the CNS in the acute phase post-injury. However, this process prevents complete tissue recovery in the late/chronic phase by producing permanent scarring, which significantly impacts brain function. Various glial cell types participate in the scar formation, but this process is mostly attributed to reactive astrocytes and microglia, which play important roles in several brain pathologies. Novel technologies including whole-genome transcriptomic and epigenomic analyses, and unbiased proteomics, show that both astrocytes and microglia represent groups of heterogenic cell subpopulations with different genomic and functional characteristics, that are responsible for their role in neurodegeneration, neuroprotection and regeneration. Depending on the representation of distinct glia subpopulations, the tissue damage as well as the regenerative processes or delayed neurodegeneration after TBI may thus differ in nearby or remote areas or in different brain structures. This review summarizes TBI as a complex process, where the resultant effect is severity-, region- and time-dependent and determined by the model of the CNS injury and the distance of the explored area from the lesion site. Here, we also discuss findings concerning intercellular signaling, long-term impacts of TBI and the possibilities of novel therapeutical approaches. We believe that a comprehensive study with an emphasis on glial cells, involved in tissue post-injury processes, may be helpful for further research of TBI and be the decisive factor when choosing a TBI model.

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Section: Long-term Impact Of Traumatic Brain Injurymentioning

confidence: 95%

Reactive gliosis in traumatic brain injury: a comprehensive review

Amlerova,

Chmelova,

Anderova

et al. 2024

Front. Cell. Neurosci.

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Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome

Barreto‐Núñez,

Béland,

Boutej

et al. 2024

Glia

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Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1‐G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age‐matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo. Proteome analysis revealed a development of two distinct molecular signatures at early and advanced stages of disease. While at early stages of disease, we identified several proteins implicated in microglia immune functions such as GPNMB, HMBOX1, at advanced stages of disease microglia signature at protein level was characterized with a robust upregulation of several unconventional proteins including rootletin, major vaults proteins and STK38. Upregulation of GPNMB and rootletin has been also found in the spinal cord samples of sporadic ALS. Remarkably, the top biological functions of microglia, in particular in the advanced disease, were not related to immunity/immune response, but were highly enriched in terms linked to RNA metabolism. Together, our results suggest that, over the course of disease, chronically activated microglia develop unconventional protein signatures and gradually lose their immune identity ultimately turning into functionally inefficient immune cells.

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Cortical glia in SOD1(G93A) mice are subtly affected by ALS-like pathology

Cited by 2 publications

References 76 publications

Reactive gliosis in traumatic brain injury: a comprehensive review

Reactive gliosis in traumatic brain injury: a comprehensive review

Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome

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