HCAR1-Mediated l-Lactate Signaling Suppresses Microglial Phagocytosis

Nicola, Raneen; Madar, Ravit; Okun, Eitan

doi:10.1007/s12017-022-08710-5

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…To achieve this, we utilized a previously described method (Erwig et al, 2019) to isolate pure myelin from the mouse brain, and labeled the myelin with pHrodo. This fluorescent dye is a pH‐sensitive probe that shows low fluorescence intensity at neutral pH but undergoes a significant increase in fluorescence upon acidification within the lysosome (Nicola et al, 2022). Subsequently, we induced in vitro phagocytosis using labeled myelin and assessed microglial phagocytic capacity (Nicola et al, 2022; Pluvinage et al, 2019) using Incucyte.…”

Section: Resultsmentioning

confidence: 99%

“…This fluorescent dye is a pH‐sensitive probe that shows low fluorescence intensity at neutral pH but undergoes a significant increase in fluorescence upon acidification within the lysosome (Nicola et al, 2022). Subsequently, we induced in vitro phagocytosis using labeled myelin and assessed microglial phagocytic capacity (Nicola et al, 2022; Pluvinage et al, 2019) using Incucyte. Real‐time live‐cell imaging allowed us to track the digestion of myelin by microglia over an 8‐hour duration.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, we induced in vitro phagocytosis using labeled myelin and assessed microglial phagocytic capacity (Nicola et al, 2022;Pluvinage et al, 2019) using Incucyte. Real-time live-cell imaging allowed us to track the digestion of myelin by microglia over an 8-hour duration.…”

Section: In Early Postnatal Gtf2i Cko Mice Diverse Microglial Activat...mentioning

confidence: 99%

“…Adult microglia were isolated as previously described (Lau et al, 2021; Moussaud & Draheim, 2010; Nicola et al, 2022) with minor modifications. Briefly, P30 mice were deeply anesthetized and perfused in the left ventricle with PBS.…”

Section: Microglia Isolation and Facsmentioning

confidence: 99%

“…For analysis, maximum intensity projections were formed from the Z-stacks. Intensity was quantified manually using ImageJ program.9 | MICROGLIA ISOLATION AND FACS9.1 | Adult microglial isolationAdult microglia were isolated as previously described(Lau et al, 2021;Moussaud & Draheim, 2010;Nicola et al, 2022) with minor modifications. Briefly, P30 mice were deeply anesthetized and perfused in the left ventricle with PBS.…”

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confidence: 99%

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Neuronal deletion of Gtf2i results in developmental microglial alterations in a mouse model related to Williams syndrome

Bar,

Fischer,

Rokach

et al. 2024

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Williams syndrome (WS) is a genetic neurodevelopmental disorder caused by a heterozygous microdeletion, characterized by hypersociability and unique neurocognitive abnormalities. Of the deleted genes, GTF2I has been linked to hypersociability in WS. We have recently shown that Gtf2i deletion from forebrain excitatory neurons, referred to as Gtf2i conditional knockout (cKO) mice leads to multi‐faceted myelination deficits associated with the social behaviors affected in WS. These deficits were potentially mediated also by microglia, as they present a close relationship with oligodendrocytes. To study the impact of altered myelination, we characterized these mice in terms of microglia over the course of development. In postnatal day 30 (P30) Gtf2i cKO mice, cortical microglia displayed a more ramified state, as compared with wild type (controls). However, postnatal day 4 (P4) microglia exhibited high proliferation rates and an elevated activation state, demonstrating altered properties related to activation and inflammation in Gtf2i cKO mice compared with control. Intriguingly, P4 Gtf2i cKO‐derived microglial cells exhibited significantly elevated myelin phagocytosis in vitro compared to control mice. Lastly, systemic injection of clemastine to P4 Gtf2i cKO and control mice until P30, led to a significant interaction between genotypes and treatments on the expression levels of the phagocytic marker CD68, and a significant reduction of the macrophage/microglial marker Iba1 transcript levels in the cortex of the Gtf2i cKO treated mice. Our data thus implicate microglia as important players in WS, and that early postnatal manipulation of microglia might be beneficial in treating inflammatory and myelin‐related pathologies.

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