Abstract
Synaptic loss is the major neuropathological correlate of memory decline as a result of Alzheimer´s Disease (AD). Synaptic failure appears to depend on the toxic actions of small and soluble amyloid-β (Aβ) oligomers. However, few studies have addressed the mechanism by which aging makes synapses more vulnerable to Aβ toxicity. In the present study we analyzed mitochondrial function and morphology and markers of oxidative stress in isolated presynaptic nerve endings from the hippocampus that were exposed to Aβ peptide at different ages. We found an age-related decline in mitochondrial activity, reduced antioxidant contents and increased oxidative stress markers in resting and depolarized synaptic terminals. Ultrastructural changes including an increase in mitochondrial size and a significant reduction of synaptic vesicles contents were also observed. In addition, synaptosomes obtained from 24 month old rats were more sensitive to Aβ toxicity. These data provide evidence of morphological and biochemical synaptic changes associated with aging that may contribute to exacerbate the damaging effects of Aβ.
Keywords: Amyloid-β protein, synaptosomes, oxidative stress, aging, hippocampus, mitochondrial dysfunction
Current Alzheimer Research
Title:Synaptic Aging is Associated with Mitochondrial Dysfunction, Reduced Antioxidant Contents and Increased Vulnerability to Amyloid-β Toxicity
Volume: 10 Issue: 3
Author(s): Ricardo Quiroz-Baez, Diana Flores-Domínguez and Clorinda Arias
Affiliation:
Keywords: Amyloid-β protein, synaptosomes, oxidative stress, aging, hippocampus, mitochondrial dysfunction
Abstract: Synaptic loss is the major neuropathological correlate of memory decline as a result of Alzheimer´s Disease (AD). Synaptic failure appears to depend on the toxic actions of small and soluble amyloid-β (Aβ) oligomers. However, few studies have addressed the mechanism by which aging makes synapses more vulnerable to Aβ toxicity. In the present study we analyzed mitochondrial function and morphology and markers of oxidative stress in isolated presynaptic nerve endings from the hippocampus that were exposed to Aβ peptide at different ages. We found an age-related decline in mitochondrial activity, reduced antioxidant contents and increased oxidative stress markers in resting and depolarized synaptic terminals. Ultrastructural changes including an increase in mitochondrial size and a significant reduction of synaptic vesicles contents were also observed. In addition, synaptosomes obtained from 24 month old rats were more sensitive to Aβ toxicity. These data provide evidence of morphological and biochemical synaptic changes associated with aging that may contribute to exacerbate the damaging effects of Aβ.
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Quiroz-Baez Ricardo, Flores-Domínguez Diana and Arias Clorinda, Synaptic Aging is Associated with Mitochondrial Dysfunction, Reduced Antioxidant Contents and Increased Vulnerability to Amyloid-β Toxicity, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030012
DOI https://dx.doi.org/10.2174/1567205011310030012 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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