Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.
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-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.
Kuchibhotla
Kishore V
KV
Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.
Lattarulo
Carli R
CR
Hyman
Bradley T
BT
Bacskai
Brian J
BJ
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D009474:Neurons / Q000473:pathology / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology
D016229:Amyloid beta-Peptides; D002118:Calcium