Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice
Open accessAbstract
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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Astrocyte Ca2+ dynamics and network responses become aberrant in mouse models of HD, AD, and ALS, possibly contributing to cognitive impairment and neuropathology.
“Astrocyte Ca2+ dynamics and network responses become aberrant in mouse models of HD53, AD54, and ALS55, possibly contributing to cognitive impairment and neuropathology43,53,56.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [54]
Optogenetics and DREADDs are potential tools to manipulate reactive astrocytes or to restore their aberrant Ca2+ signaling observed in mouse models of neurodegenerative diseases.
“Optogenetics25 and designer receptors exclusively activated by designer drugs (DREADDs)25 are potential tools to manipulate reactive astrocytes or to restore their aberrant Ca2+ signaling observed in mouse models of neurodegenerative diseases53–55.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [54]
Astrocytes in apposition to Aβ deposits are hyperactive and display higher resting Ca2+ levels, more frequent and larger Ca2+ elevations, long-range coordinated Ca2+ waves never seen in control mice, and increased gliotransmission.
“Interestingly, astrocytes in apposition to Aβ deposits are also 'hyperactive' and display higher resting Ca 2+ level, more frequent and larger Ca 2+ elevations, long-range coordinated Ca 2+ waves that are never seen in control mice 95, 98, 111 , as well as increased gliotranmission 112 .”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [111]
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- [3]Spires TL J Neurosci 2005 Aug 3 25 7278 16079410 PMC1820616
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- [26]Supporting Online Material www.sciencemag.org Materials and Methods Figs. S1–S6 Movie S1, S2
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- Authors
- Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T., & Bacskai, B. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Bacskai, Brian J.
- Venue
- Science
- Published
- 2009-02-27
- Volume
- 323
- Issue
- 5918
- Pages
- 1211-1215
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2884172
- OpenAlex
- W2027616725
- Cited by
- 729
- References
- 24
- Citations by year
- 2026: 29 · 2025: 37 · 2024: 38 · 2023: 54 · 2022: 34 · 2021: 51 · 2020: 53 · 2019: 38 · 2018: 43 · 2017: 39 · 2016: 40 · 2015: 46 · 2014: 41 · 2013: 42 · 2012: 39
- FWCI
- 31.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG008487, P50AG005134, P30AG062421)
- National Institute of Neurological Disorders and Stroke (F31NS058075, NS580752)
- National Institute of Biomedical Imaging and Bioengineering (EB 000768, R01EB000768)
- National Center for Research Resources (S10RR025645)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, astrocytes, intercellular calcium waves, amyloid plaques, calcium transients
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Calcium, Disease Models, Animal, Homeostasis, Humans, Mice, Transgenic, Neurons, Amyloid beta-Peptides, Calcium Signaling, Microscopy, Fluorescence, Multiphoton, Mice, Plaque, Amyloid
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