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04:41
Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
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Aβ42 oligomers selectively disrupt neuronal calcium release
Cristian Lazzari1, Maulilio J Kipanyula1, Mario Agostini1
1Department of Biomedical Sciences, University of Padua, Padua, Italy.
Neurobiology of Aging
|December 3, 2014
Summary
Alzheimer's disease (AD) involves amyloid-beta (Aβ) peptides disrupting calcium (Ca2+) homeostasis. Aβ42 oligomers, not monomers, alter Ca2+ release from stores, indicating a potential therapeutic target for AD dementia.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Amyloid-beta (Aβ) peptide accumulation is linked to aging and Alzheimer's disease (AD) progression.
- Aβ peptides contribute to synaptic dysfunction, memory deficits, and intracellular calcium (Ca2+) homeostasis disruption.
Purpose of the Study:
- To investigate the short-term effects of synthetic amyloid-beta 42 (Aβ42) on neuronal Ca2+ dynamics.
- To determine the specific mechanisms by which Aβ42 influences Ca2+ release and homeostasis in neurons.
Main Methods:
- Neuronal cytosolic and endoplasmic reticulum Ca2+ measurements were performed.
- Acute application of Aβ42 (oligomers and monomers) at submicromolar concentrations.
- Assessment of resting Ca2+ levels and KCl-induced Ca2+ influx after Aβ42 treatment.
- Evaluation of inositol 1,4,5-trisphosphate (IP3)- and caffeine-induced Ca2+ mobilization.
Main Results:
- Aβ42 monomers and oligomers did not induce acute Ca2+ release or influx.
- Aβ42 treatment did not alter resting cytosolic Ca2+ or depolarization-induced Ca2+ influx.
- Aβ42 oligomers, but not monomers, altered Ca2+ release from stores, affecting IP3- and caffeine-induced mobilization without changing total store content.
- Aβ42 oligomer-induced Ca2+ dysregulation involves metabotropic glutamate receptor 5 and requires network activity and exo-endocytosis.
Conclusions:
- Ca2+ store dysfunction is directly implicated in Aβ42 neurotoxicity.
- Aβ42 oligomers specifically disrupt neuronal Ca2+ handling, distinct from monomers.
- Targeting Ca2+ store dysfunction presents a potential therapeutic strategy for Alzheimer's disease-like dementia.
Keywords:
Alzheimer's diseaseAβ42 monomersAβ42 oligomersCalcium storesERD4 cameleonEndoplasmic reticulumFura-2Mouse cortical neuronsMore Related Videos
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