Chemogenetic activation of microglial Gi signaling decreases microglial surveillance and impairs neuronal synchronization

Science Advances, Год журнала: 2025, Номер 11(9)

Опубликована: Фев. 28, 2025

Microglia actively survey the brain and dynamically interact with neurons to maintain homeostasis. Microglial Gi protein–coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, impact of temporally activating microglial signaling on dynamics neuronal activity homeostatic remains largely unknown. In this study, we used Gi-based designer exclusively activated by drugs (Gi-DREADD) selectively modulate pathway. By integrating chemogenetic approach vivo two-photon imaging, observed that exogenous activation transiently inhibited process dynamics, reduced activity, impaired synchronization. These altered functions were associated decrease interactions between microglia neuron somata. Together, study demonstrates acute, regulates circuit function, offering potential pharmacological target for neuromodulation through microglia.

Язык: Английский

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Microglia replacement effectively attenuates the disease progress of ALSP in the mouse model and human patient

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 11, 2024

Abstract Microglia play critical roles in the brain physiology and pathology. CSF1R is primarily expressed microglia. The mono-allelic mutation causes adult-onset leukoencephalopathy with axonal spheroids pigmented glia (ALSP), a lethal neurological disease no rational cure clinical trials. There are animal models mimicking human ALSP. In this study, we first developed mouse based on ALSP hotspot mutations. We then utilized microglia replacement by bone marrow transplantation (Mr BMT) to replace Csf1r -deficient mice -normal donor cells. With pathogenic gene correction, Mr BMT efficiently attenuated pathologies. Previously, an patient received traditional (tBMT) due misdiagnosis of metachromatic leukodystrophy. progress was halted for 15 years unknown reasons. demonstrated that tBMT equivalent or close BMT, achieving efficient therefore attenuating model. Next, applied patients. Our results show after replacement, course effectively halted. Together, corrects thus halts model This study strongly demonstrates potentials treatments.

Язык: Английский

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Astrocyte morphological remodeling regulates consciousness state transitions induced by inhaled general anesthesia

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma

Cell chemical biology, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

Язык: Английский

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Noninvasive Light Flicker Stimulation Promotes Optic Nerve Regeneration by Activating Microglia and Enhancing Neural Plasticity in Zebrafish

Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(5), С. 3 - 3

Опубликована: Май 1, 2024

Forty-hertz light flicker stimulation has been proven to reduce neurodegeneration, but its effect on optic nerve regeneration is unclear. This study explores the of 40-Hz in promoting zebrafish and investigates underlying mechanisms.

Язык: Английский

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Immunology reshapes neuroscience, and neuroscience reshapes immunology

Fundamental Research, Год журнала: 2024, Номер 4(2), С. 199 - 200

Опубликована: Янв. 21, 2024

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Myelin modulates the process of isoflurane anesthesia through the regulation of neural activity

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(8)

Опубликована: Авг. 1, 2024

Abstract Aims The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed critical roles of myelin and oligodendrocytes (OLs) in higher functions brain. However, it is unknown whether actively participates regulation GA. aim this study to investigate possible mechanisms consciousness alterations isoflurane anesthesia. Methods First, demyelination models for entire brain specific neural nuclei were established potential role myelination GA, as well its regional specificity. c‐Fos staining was then performed on demyelinated verify impact loss neuronal activity. Finally, activity neurons during anesthesia mice recorded optical fiber photometric calcium signal. related behavioral indicators EEG analyzed. Results A prolonged emergence time observed from mice, which suggested involvement regulating distinct LPC further clarified region‐specific myelin. effect certain nucleus consistent with that towards we found modulation possibly through Conclusions In brief, plays an essential process modification integrity Our findings enhanced comprehension function, offered a fresh perspective investigating

Язык: Английский

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A Neuronal Activity-Boosting Microglial Function in Post-Anesthetic Emergence: How Microglial-Neuronal Crosstalk May Alter States of Consciousness

Neuroscience Bulletin, Год журнала: 2024, Номер 40(10), С. 1590 - 1592

Опубликована: Авг. 27, 2024

Язык: Английский

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Maestros of anesthesia

eLife, Год журнала: 2024, Номер 13

Опубликована: Янв. 18, 2024

Microglia regulate anesthesia by altering the activity of neurons in specific regions brain via a purinergic receptor.

Язык: Английский

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Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia

Purinergic Signalling, Год журнала: 2024, Номер 20(6), С. 573 - 575

Опубликована: Май 9, 2024

Язык: Английский

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