Cholesterol-induced robust Ca oscillation in astrocytes required for survival and lipid droplet formation in high-cholesterol condition

Adachi, Chihiro; Otsuka, Shio; Inoue, Takafumi

doi:10.1016/j.isci.2022.105138

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…Reactive astrogliosis has a persistent role in disease progression through various mechanisms; it inhibits remyelination and axonal regeneration by forming glial scars and increasing sensitivity to ATP and elevated calcium oscillations 40 , 41 . In a prior study, excess extracellular cholesterol in the environment—which can be attributed to demyelination—led to elevated calcium oscillations in astroglia that were partially mediated by HC activity; however, it did not have this effect in microglia or neurons 42 . Another study has emphasized the importance of elevated calcium levels at EAE onset, reporting that Th17 cells are able to migrate within the leptomeninges while consistently exhibiting calcium signaling 43 .…”

Section: Discussionmentioning

confidence: 83%

Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

Takase,

Yamasaki,

Nagata

et al. 2024

Sci Rep

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In chronic stages of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalitis (EAE), connexin (Cx)43 gap junction channel proteins are overexpressed because of astrogliosis. To elucidate the role of increased Cx43, the central nervous system (CNS)-permeable Cx blocker INI-0602 was therapeutically administered. C57BL6 mice with chronic EAE initiated by MOG35-55 received INI-0602 (40 mg/kg) or saline intraperitoneally every other day from days post-immunization (dpi) 17–50. Primary astroglia were employed to observe calcein efflux responses. In INI-0602-treated mice, EAE clinical signs improved significantly in the chronic phase, with reduced demyelination and decreased CD3+ T cells, Iba-1+ and F4/80+ microglia/macrophages, and C3+GFAP+ reactive astroglia infiltration in spinal cord lesions. Flow cytometry analysis of CD4+ T cells from CNS tissues revealed significantly reduced Th17 and Th17/Th1 cells (dpi 24) and Th1 cells (dpi 50). Multiplex array of cerebrospinal fluid showed significantly suppressed IL-6 and significantly increased IL-10 on dpi 24 in INI-0602-treated mice, and significantly suppressed IFN-γ and MCP-1 on dpi 50 in the same group. In vitro INI-0602 treatment inhibited ATP-induced calcium propagations of Cx43+/+ astroglial cells to similar levels of those of Cx43−/− cells. Astroglial Cx43 hemichannels represent a novel therapeutic target for chronic EAE and MS.

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Section: Discussionmentioning

confidence: 83%

Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

Takase,

Yamasaki,

Nagata

et al. 2024

Sci Rep

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“…In studies of Fmr1 KO mouse astrocytes, cholesterol, and desmosterol (the last precursor of cholesterol in the Bloch pathway) accumulated in astrocytes ( Talvio et al, 2023 ). Here, cholesterol levels did not differ between human or mouse FMRP-deficient and control astrocyte conditioned medium, suggesting that astrocytes maintained extracellular cholesterol homeostasis to avoid cholesterol toxicity ( Adachi et al, 2022 ; Talvio et al, 2023 ). Both mouse and human FMRP-deficient astrocytes expressed less ATP-binding cassette transporter A1 (ABCA1, the main astrocytic cholesterol exporter) than their respective controls.…”

Section: Altered Lipidome Of Fxs Astrocytesmentioning

confidence: 80%

Astrocytes in fragile X syndrome

Talvio,

Castrén

2024

Front. Cell. Neurosci.

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Astrocytes have an important role in neuronal maturation and synapse function in the brain. The interplay between astrocytes and neurons is found to be altered in many neurodevelopmental disorders, including fragile X syndrome (FXS) that is the most common inherited cause of intellectual disability and autism spectrum disorder. Transcriptional, functional, and metabolic alterations in Fmr1 knockout mouse astrocytes, human FXS stem cell-derived astrocytes as well as in in vivo models suggest autonomous effects of astrocytes in the neurobiology of FXS. Abnormalities associated with FXS astrocytes include differentiation of central nervous system cell populations, maturation and regulation of synapses, and synaptic glutamate balance. Recently, FXS-specific changes were found more widely in astrocyte functioning, such as regulation of inflammatory pathways and maintenance of lipid homeostasis. Changes of FXS astrocytes impact the brain homeostasis and function both during development and in the adult brain and offer opportunities for novel types of approaches for intervention.

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“…The dish was placed on an inverted fluorescence microscope (IX71, Olympus, Tokyo, Japan) with a 20x objective lens (UApo/340, 0.75, Olympus) and a CCD camera (ORCA-ER, Hamamatsu Photonics, Hamamatsu, Japan) [ 11 ]. Fura 2-AM was excited alternately every 3 s using two wavelengths (340 nm and 380 nm) of excitation light from a xenon lamp that passed through an excitation filter (FF01-340/26-25 (OPTO-LINE, Saitama, Japan) for 340 nm and MBP380 (Olympus) for 380 nm) [ [11] , [12] , [13] ]. The light transmitted through a beam splitter (400 nm, DM400 (Olympus)) and an emission filter (420 nm, BA420 (Olympus)) was captured by a cooled CCD camera.…”

Section: Methodsmentioning

confidence: 99%

Development of the observation of membrane fusion with label-free liposomes by calcium imaging

Hotta

Hayase

Kitanaka

et al. 2023

Biochemistry and Biophysics Reports

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Cholesterol-induced robust Ca oscillation in astrocytes required for survival and lipid droplet formation in high-cholesterol condition

Cited by 4 publications

References 68 publications

Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model

Astrocytes in fragile X syndrome

Development of the observation of membrane fusion with label-free liposomes by calcium imaging

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