Faculty, Staff and Student Publications

Language

English

Publication Date

7-17-2024

Journal

Journal of Neuroinflammation

DOI

10.1186/s12974-024-03169-6

PMID

39020359

PMCID

PMC11256502

PubMedCentral® Posted Date

7-17-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Key functions of Ca2+ signaling in rodent microglia include monitoring the brain state as well as the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca2+ dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca2+ signal properties of human microglia remain unknown.

Methods: We developed a novel genetically-encoded ratiometric Ca2+ indicator, targeting microglial cells in the freshly resected human tissue, organotypically cultured tissue slices and analyzed in situ ongoing Ca2+ signaling of decades-old microglia dwelling in their native microenvironment.

Results: The data revealed marked compartmentalization of Ca2+ signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca2+ levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca2+ signaling, the fraction and the amplitude of process Ca2+ signals and the duration of somatic Ca2+ signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca2+ signals and the duration of process Ca2+ signals increased along this pathway.

Keywords

Microglia, Humans, Calcium Signaling, Calcium, Male, Female, Cells, Cultured, Human microglia, In vitro human brain tissue model, Native microglial microenvironment, Morphotypes of resident microglia, microRNA-9-assisted labeling

Published Open-Access

yes

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