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Alzheimer's amyloid beta-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes
- Source :
- Neuromolecular medicine. 3(3)
- Publication Year :
- 2003
-
Abstract
- Alzheimer's disease (AD) involves the progressive extracellular deposition of amyloid beta-peptide (Abeta), a self-aggregating 40-42 amino acid protein that can damage neurons resulting in their dysfunction and death. Studies of neurons have shown that Abeta perturbs cellularcalcium homeostasis so that calcium responses to agonists that induce calcium influx or release from internal stores are increased. The recent discovery of intercellular calcium waves in astrocytes suggests intriguing roles for astrocytes in the long-range transfer of information in the nervous system. We now report that Abeta alters calcium-wave signaling in cultured rat cortical astrocytes. Exposure of astrocytes to Abeta1-42 resulted in an increase in the amplitude and velocity of evoked calcium waves, and increased the distance the waves traveled. Suramin decreased wave propagation in untreated astrocytes and abrogated the enhancing effect of Abeta on calciumwave amplitude and velocity, indicating a requirement for extracellular ATP in wave propagation. Treatment of astrocytes with an uncoupler of gap junctions did not significantly reduce the amplitude, velocity, or distance of calcium waves in control cultures, but completely abolished the effects of Abeta on each of the three wave parameters. These findings reveal a novel action of Abeta on the propagation of intercellular calcium signals in astrocytes, and also suggests a role for altered astrocyte calcium-signaling in the pathogenesis of AD.
- Subjects :
- Octanols
Amyloid
chemistry.chemical_element
Connexin
Glutamic Acid
Cell Communication
Suramin
Calcium
Biology
Membrane Potentials
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
Adenosine Triphosphate
Alzheimer Disease
medicine
Extracellular
Animals
Calcium Signaling
Cerebral Cortex
Amyloid beta-Peptides
Cell Membrane
Glutamate receptor
Gap junction
Gap Junctions
Peptide Fragments
Cell biology
Rats
Up-Regulation
medicine.anatomical_structure
Neurology
chemistry
Animals, Newborn
Astrocytes
Molecular Medicine
Calcium Channels
Extracellular Space
Neuroscience
Homeostasis
Astrocyte
Subjects
Details
- ISSN :
- 15351084
- Volume :
- 3
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Neuromolecular medicine
- Accession number :
- edsair.doi.dedup.....764912333610c7bd2f4ec5ba8693d457