Intracellular Ca2(+) dynamics are required for microglial process motility during surveillance and in response to injury

Tiwari, Sagun; Zeng, Fan; Zhou, Yan; Chok, Alaa; Brazhe, Alexey; Semyanov, Alexey; Zhu, Kaichuan; Xiang, Xianyuan; Kettenmann, Helmut

Intracellular Ca2(+) dynamics are required for microglial process motility during surveillance and in response to injury

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Item Type:	Article
Title:	Intracellular Ca2(+) dynamics are required for microglial process motility during surveillance and in response to injury
Creators:	Tiwari, Sagun, Zeng, Fan, Zhou, Yan, Chok, Alaa, Brazhe, Alexey, Semyanov, Alexey, Zhu, Kaichuan, Xiang, Xianyuan and Kettenmann, Helmut ORCID: https://orcid.org/0000-0001-8208-0291
Abstract:	Microglia, the resident immune cells of the central nervous system, play pivotal roles in brain surveillance and injury responses through highly dynamic process motility. Here, we investigated the role of Ca2(+) signaling in mediating microglial process motility under both physiological and pathological conditions in vivo. Using dual-laser two-photon microscopy in a transgenic mouse model expressing red fluorescent protein (mCherry) and the Ca2(+) indicator (GCaMP6m) specifically in microglia, we observed autonomous Ca2(+) microdomains that operate asynchronously within individual processes, exhibiting significantly more frequent and localized Ca2(+) transients compared to non-motile structures. Upon focal laser-induced cortical injury, we observed rapid Ca2(+) waves in microglia, with processes extending toward the lesion site displaying correlated Ca2(+) activity. Attenuation of Ca2(+) transients by BAPTA-AM, a Ca2(+) chelator, impaired both homeostatic and laser-induced motility. Importantly, microglia-specific genetic overexpression of plasma membrane Ca2(+) ATPase 2 in vivo markedly reduced both homeostatic surveillance and injury-induced motility. Together, our findings provide evidence that microglial intracellular Ca2(+) signaling is required for process motility in vivo, supporting a model in which local Ca2(+) dynamics enable surveillance and injury-directed remodeling.
Keywords:	Microglia, Ca2(+) Signaling, Surveillance, Motility, In Vivo, Ca2(+) Wave, Laser Injury, PMCA2
Source:	Journal of Neuroinflammation
ISSN:	1742-2094
Publisher:	BioMed Central
Date:	7 September 2026
Official Publication:	https://doi.org/10.1186/s12974-026-04013-9

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