TY - JOUR
T1 - Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice
AU - Kuchibhotla, Kishore V.
AU - Lattarulo, Carli R.
AU - Hyman, Bradley T.
AU - Bacskai, Brian J.
PY - 2009/2/27
Y1 - 2009/2/27
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1169096
DO - 10.1126/science.1169096
M3 - Article
C2 - 19251629
AN - SCOPUS:61349096009
SN - 0036-8075
VL - 323
SP - 1211
EP - 1215
JO - Science
JF - Science
IS - 5918
ER -