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Oxidative medicine and cellular longevity
2012;2012 843649.

Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: a protective role for melatonin.

Sergio Rosales-Corral, Dario Acuna-Castroviejo, Dun Xian Tan, Gabriela López-Armas, José Cruz-Ramos, Rubén Munoz, Valery G Melnikov, Lucien C Manchester, Russel J Reiter
Author Information
  1. Sergio Rosales-Corral: Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Sierra Mojada 800 Colonia Independencia, 44340 Guadalajara, JAL, Mexico. rosalescorra@uthscsa.edu
PMID: 22666521 DOI: 10.1155/2012/843649

Abstract

Amyloid-beta (Aβ) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer's disease (AD) brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell. Thereafter, Aβ appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance.

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MeSH Term

Adenosine Triphosphatases
Amyloid beta-Peptides
Animals
Axons
Cell Respiration
Cholesterol
Extracellular Space
Hippocampus
Hydrolysis
Injections, Intraventricular
Male
Melatonin
Membrane Fluidity
Mice
Mitochondria
Mitochondrial Membranes
Nerve Degeneration
Oxidative Stress
Protective Agents
Protein Structure, Quaternary
Rats
Rats, Wistar
Reactive Oxygen Species

Chemicals

Amyloid beta-Peptides
Protective Agents
Reactive Oxygen Species
Cholesterol
Adenosine Triphosphatases
Melatonin
Journal Article

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