Journal of Neuroinflammation (Jul 2024)

Morphotype-specific calcium signaling in human microglia

  • Sofia Nevelchuk,
  • Bianca Brawek,
  • Niklas Schwarz,
  • Ariel Valiente-Gabioud,
  • Thomas V. Wuttke,
  • Yury Kovalchuk,
  • Henner Koch,
  • Anke Höllig,
  • Frederik Steiner,
  • Katherine Figarella,
  • Oliver Griesbeck,
  • Olga Garaschuk

DOI
https://doi.org/10.1186/s12974-024-03169-6
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 18

Abstract

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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.

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