Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice

Kishore V. Kuchibhotla, Carli R. Lattarulo, Bradley T. Hyman, Brian J. Bacskai

Research output: Contribution to journalArticle

Abstract

Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-β plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-β deposits, there exists a more general astrocyte-based network response to focal pathology.

Original languageEnglish (US)
Pages (from-to)1211-1215
Number of pages5
JournalScience
Volume323
Issue number5918
DOIs
StatePublished - Feb 27 2009
Externally publishedYes

ASJC Scopus subject areas

  • General

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