TY - JOUR
T1 - Accumulation of exogenous amyloid- Beta peptide in hippocampal mitochondria causes their dysfunction
T2 - A protective role for melatonin
AU - Rosales-Corral, Sergio
AU - Acuna-Castroviejo, Dario
AU - Tan, Dun-Xian
AU - López-Armas, Gabriela
AU - Cruz-Ramos, José
AU - Munoz, Rubén
AU - Melnikov, Valery G.
AU - Manchester, Lucien C.
AU - Reiter, Russel J.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862285962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862285962&partnerID=8YFLogxK
U2 - 10.1155/2012/843649
DO - 10.1155/2012/843649
M3 - Article
C2 - 22666521
AN - SCOPUS:84862285962
SN - 1942-0900
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 843649
ER -