Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice

By K. Kuchibhotla, Carli R. Lattarulo, Bradley T. Hyman, B. Bacskai. Science, 2009

721 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/1efbfe443ec5fedd7de3365b4fbd4008bf840924

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. M. Pekny
2. M. Sofroniew
3. M. Pekna
4. L. Mucke
5. E. Hol
6. J. Palop
7. Alexei Verkhratsky
8. David Attwell

In Neurology

1. M. Pekny
2. M. Pekna
3. M. Sofroniew
4. E. Hol
5. Alexei Verkhratsky
6. David Attwell
7. E. A. Newman
8. L. Mucke

In Physiology

1. L. Mucke
2. J. Palop
3. M. Pekny
4. M. Pekna
5. David Attwell
6. E. A. Newman
7. Alexei Verkhratsky
8. E. Hol

Citations in the corpus

• Astrocytes: a central element in neurological diseases (2016, background): “In an AD mouse model a hyperactivity in intracellular calcium waves in astrocytes near Aβ plaques have been observed [119]; whereas β-amyloid was shown to alter astroglial Ca2+ signalling kit [74, 188], see also [136] for detailed overview of glial calcium signalling in AD.”
• Fluorescence lifetime imaging – techniques and applications (2012, methodology): “Effects used in FLIM applications are: • Quenching of the fluorescence or phosphorescence by various ions, especially Ca2+ and Cl−, both of which are important to the function of the neuronal system (Kaneko et al., 2004; Gilbert et al., 2007; Funk et al., 2008; Kuchibhotla et al., 2009).”
• Amyloid-β Induced Neuronal Dysfunction in Alzheimer’s Disease: From Synapses toward Neural Networks (2010, background): “Of note, astrocytes from hAPP/PS1 mice have synchronous hyperactivity in [Ca 2+ ] i transients across long distances that is uncoupled from neuronal activit”
• Glial and neuronal control of brain blood flow (2010, positive): “A raised basal [Ca 2+ ] i and enhanced occurrence of spontaneous Ca 2+ waves in the astrocytes of mice with amyloid-β plaque”
• Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders (2011, neutral): “Astrocytes regulate the contractility of intracerebral arterie”