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  1. Article: Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

    Garland, Emma F / Hartnell, Iain J / Boche, Delphine

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 824888

    Abstract: Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood-brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of ... ...

    Abstract Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood-brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs,
    Language English
    Publishing date 2022-02-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.824888
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The mitochondrial protein TSPO in Alzheimer's disease: relation to the severity of AD pathology and the neuroinflammatory environment.

    Garland, Emma F / Dennett, Oliver / Lau, Laurie C / Chatelet, David S / Bottlaender, Michel / Nicoll, James A R / Boche, Delphine

    Journal of neuroinflammation

    2023  Volume 20, Issue 1, Page(s) 186

    Abstract: The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer's disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due ... ...

    Abstract The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer's disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due to the absence of AD pathology and lower levels of TSPO. However, using the cerebellum as a pseudo-reference region is debated, with other brain regions suggested as more suitable. This paper aimed to establish the neuroinflammatory differences between the temporal cortex and cerebellar cortex, including TSPO expression. Using 60 human post-mortem samples encompassing the spectrum of Braak stages (I-VI), immunostaining for pan-Aβ, hyperphosphorylated (p)Tau, TSPO and microglial proteins Iba1, HLA-DR and MSR-A was performed in the temporal cortex and cerebellum. In the cerebellum, Aβ but not pTau, increased over the course of the disease, in contrast to the temporal cortex, where both proteins were significantly increased. TSPO increased in the temporal cortex, more than twofold in the later stages of AD compared to the early stages, but not in the cerebellum. Conversely, Iba1 increased in the cerebellum, but not in the temporal cortex. TSPO was associated with pTau in the temporal cortex, suggesting that TSPO positive microglia may be reacting to pTau itself and/or neurodegeneration at later stages of AD. Furthermore, the neuroinflammatory microenvironment was examined, using MesoScale Discovery assays, and IL15 only was significantly increased in the temporal cortex. Together this data suggests that the cerebellum maintains a more homeostatic environment compared to the temporal cortex, with a consistent TSPO expression, supporting its use as a pseudo-reference region for quantification in TSPO PET scans.
    MeSH term(s) Humans ; Alzheimer Disease/pathology ; Neuroinflammatory Diseases ; Mitochondrial Proteins/metabolism ; Brain/metabolism ; Microglia/metabolism ; Positron-Emission Tomography/methods ; Receptors, GABA/metabolism
    Chemical Substances Mitochondrial Proteins ; Receptors, GABA ; TSPO protein, human
    Language English
    Publishing date 2023-08-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2156455-3
    ISSN 1742-2094 ; 1742-2094
    ISSN (online) 1742-2094
    ISSN 1742-2094
    DOI 10.1186/s12974-023-02869-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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