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  1. Article ; Online: Astrocytes at the intersection of ageing, obesity, and neurodegeneration.

    Firth, Wyn / Pye, Katherine R / Weightman Potter, Paul G

    Clinical science (London, England : 1979)

    2024  Volume 138, Issue 8, Page(s) 515–536

    Abstract: Once considered passive cells of the central nervous system (CNS), glia are now known to actively maintain the CNS parenchyma; in recent years, the evidence for glial functions in CNS physiology and pathophysiology has only grown. Astrocytes, a ... ...

    Abstract Once considered passive cells of the central nervous system (CNS), glia are now known to actively maintain the CNS parenchyma; in recent years, the evidence for glial functions in CNS physiology and pathophysiology has only grown. Astrocytes, a heterogeneous group of glial cells, play key roles in regulating the metabolic and inflammatory landscape of the CNS and have emerged as potential therapeutic targets for a variety of disorders. This review will outline astrocyte functions in the CNS in healthy ageing, obesity, and neurodegeneration, with a focus on the inflammatory responses and mitochondrial function, and will address therapeutic outlooks.
    MeSH term(s) Humans ; Astrocytes/metabolism ; Obesity/physiopathology ; Obesity/metabolism ; Neurodegenerative Diseases/physiopathology ; Neurodegenerative Diseases/metabolism ; Aging/physiology ; Animals ; Mitochondria/metabolism
    Language English
    Publishing date 2024-04-23
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20230148
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.220: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Impact of chemogenetic activation of dorsal vagal complex astrocytes in mice on adaptive glucoregulatory responses.

    MacDonald, Alastair J / Pye, Katherine R / Beall, Craig / Ellacott, Kate L J

    Journal of neuroendocrinology

    2023  Volume 35, Issue 8, Page(s) e13315

    Abstract: The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo ... ...

    Abstract The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons to low glucose is conditional on intact astrocyte signalling in slice preparations, suggesting astrocytes are primary sensors of glucose deprivation (glucoprivation). Based on these published findings we hypothesised that in vivo DVC astrocyte manipulation with chemogenetics would be sufficient to alter physiological responses that control blood glucose. We found that 2-h after systemic 2-DG-induced glucoprivation there were no observable changes in morphology of glial fibrillary acidic protein (GFAP)-immunoreactive DVC cells, specifically those in the nucleus of the solitary tract (NTS). Chemogenetic activation of DVC astrocytes was sufficient to suppress nocturnal food intake by reducing both meal size and meal number and this manipulation also suppressed 2-DG-induced glucoprivic food intake. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice, chemogenetic DVC astrocyte activation did not alter glucose tolerance. In female mice, the initial glucose excursion was reduced in a glucose tolerance test, suggesting enhanced glucose absorption. Based on our data and published work, we propose that DVC astrocytes may play an indispensable homeostatic role, that is, are necessary to maintain the function of glucoregulatory neuronal circuitry, but alone their bulk activation is not sufficient to result in adaptive glucoregulatory responses. It is possible that there are state-dependent effects and/or DVC astrocyte subsets that have this specialised role, but this was unresolvable using the experimental approaches employed here.
    MeSH term(s) Male ; Female ; Mice ; Animals ; Blood Glucose ; Astrocytes/metabolism ; Vagus Nerve/physiology ; Glucose/metabolism ; Hypoglycemia/metabolism
    Chemical Substances Blood Glucose ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-06-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1007517-3
    ISSN 1365-2826 ; 0953-8194
    ISSN (online) 1365-2826
    ISSN 0953-8194
    DOI 10.1111/jne.13315
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2634: Show issues Location:
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  3. Article ; Online: Regulation of astrocyte metabolism by mitochondrial translocator protein 18 kDa.

    Firth, Wyn / Robb, Josephine L / Stewart, Daisy / Pye, Katherine R / Bamford, Rosemary / Oguro-Ando, Asami / Beall, Craig / Ellacott, Kate L J

    Journal of neurochemistry

    2024  

    Abstract: The mitochondrial translocator protein 18 kDa (TSPO) has been linked to functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in Leydig cells and microglia ... ...

    Abstract The mitochondrial translocator protein 18 kDa (TSPO) has been linked to functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in Leydig cells and microglia indicate that TSPO function may vary between cells depending on their specialized roles. Astrocytes are critical for providing trophic and metabolic support in the brain. Recent work has highlighted that TSPO expression increases in astrocytes under inflamed conditions and may drive astrocyte reactivity. Relatively little is known about the role TSPO plays in regulating astrocyte metabolism and whether this protein is involved in immunometabolic processes in these cells. Using TSPO-deficient (TSPO
    Language English
    Publishing date 2024-03-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.16089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ui II Zs.170: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Regulation of astrocyte metabolism by mitochondrial translocator protein 18kDa.

    Firth, Wyn / Robb, Josephine L / Stewart, Daisy / Pye, Katherine R / Bamford, Rosemary / Oguro-Ando, Asami / Beall, Craig / Ellacott, Kate Lj

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The mitochondrial translocator protein 18kDa (TSPO) has been linked to a variety of functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in the periphery using ... ...

    Abstract The mitochondrial translocator protein 18kDa (TSPO) has been linked to a variety of functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in the periphery using Leydig cells and hepatocytes, as well as work in microglia, indicate that the function of TSPO may vary between cells depending on their specialised roles. Astrocytes are critical for providing trophic and metabolic support in the brain as part of their role in maintaining brain homeostasis. Recent work has highlighted that TSPO expression increases in astrocytes under inflamed conditions and may drive astrocyte reactivity. However, relatively little is known about the role TSPO plays in regulating astrocyte metabolism and whether this protein is involved in immunometabolic processes in these cells. Using TSPO-deficient (TSPO
    Language English
    Publishing date 2023-10-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.29.560159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.

    Cruz, Ana M / Partridge, Katie M / Malekizadeh, Yasaman / Vlachaki Walker, Julia M / Weightman Potter, Paul G / Pye, Katherine R / Shaw, Simon J / Ellacott, Kate L J / Beall, Craig

    Frontiers in endocrinology

    2021  Volume 12, Page(s) 697445

    Abstract: Aim: We evaluated the efficacy of a novel brain permeable "metformin-like" AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.: Materials and methods: We used glucose sensing hypothalamic GT1-7 neuronal cells and ... ...

    Abstract Aim: We evaluated the efficacy of a novel brain permeable "metformin-like" AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.
    Materials and methods: We used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.
    Results: In vitro
    Conclusions: These data demonstrate that peripheral administration of the brain permeable "metformin-like" AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.
    Language English
    Publishing date 2021-12-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2021.697445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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