TY - JOUR

T1 - Antioxidant SkQ1 alleviates signs of alzheimer’s disease-like pathology in old OXYS rats by reversing mitochondrial deterioration

AU - Kolosova, Nataliya G.

AU - Tyumentsev, Mikhail A.

AU - Muraleva, Natalia A.

AU - Kiseleva, Elena

AU - Vitovtov, Anton O.

AU - Stefanova, Natalia A.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Mitochondrial dysfunction is called the missing link between brain aging and Alzheimer’s disease (AD), the most common type of age-related dementia worldwide. Among the most advanced and promising of approaches to prevention or slowing of AD are therapeutic strategies targeting mitochondria. Objective: Mitochondria-targeted antioxidant SkQ1 can suppress the development of AD signs, but its therapeutic potential in AD at clinical stages is currently unknown. Method: Using OXYS rats that simulate key characteristics of sporadic AD, we evaluated effects of SkQ1 treatment from the age of 19 to 24 months on the locomotor and exploratory activities, signs of neurodegeneration detectable by magnetic resonance imaging (MRI), amyloid-β (Aβ) protein levels in the hippocampus and serum, and structure of the mitochondrial apparatus in hippocampal neurons. Results: Treatment with SkQ1 increased behavioral activity in OXYS and Wistar (control) rats. According to MRI, SkQ1 decreased the percentage of animals with demyelination only among Wistar rats. At the same time, the antioxidant reduced hippocampal Аβ1-40 and Аβ1-42 protein levels in both rat strains and did not affect serum Аβ levels. The number of mitochondria was significantly lower in OXYS rats; SkQ1 had no effect on this parameter but significantly reduced the destructive changes in mitochondria of both rat strains. As a result, in OXYS rats, the proportion of severely damaged mitochondria decreased, whereas in Wistar rats, the proportion of intact mitochondria increased. Conclusion: According to our past and present results, the repair of the mitochondrial apparatus by SkQ1 is a promising strategy against AD.

AB - Background: Mitochondrial dysfunction is called the missing link between brain aging and Alzheimer’s disease (AD), the most common type of age-related dementia worldwide. Among the most advanced and promising of approaches to prevention or slowing of AD are therapeutic strategies targeting mitochondria. Objective: Mitochondria-targeted antioxidant SkQ1 can suppress the development of AD signs, but its therapeutic potential in AD at clinical stages is currently unknown. Method: Using OXYS rats that simulate key characteristics of sporadic AD, we evaluated effects of SkQ1 treatment from the age of 19 to 24 months on the locomotor and exploratory activities, signs of neurodegeneration detectable by magnetic resonance imaging (MRI), amyloid-β (Aβ) protein levels in the hippocampus and serum, and structure of the mitochondrial apparatus in hippocampal neurons. Results: Treatment with SkQ1 increased behavioral activity in OXYS and Wistar (control) rats. According to MRI, SkQ1 decreased the percentage of animals with demyelination only among Wistar rats. At the same time, the antioxidant reduced hippocampal Аβ1-40 and Аβ1-42 protein levels in both rat strains and did not affect serum Аβ levels. The number of mitochondria was significantly lower in OXYS rats; SkQ1 had no effect on this parameter but significantly reduced the destructive changes in mitochondria of both rat strains. As a result, in OXYS rats, the proportion of severely damaged mitochondria decreased, whereas in Wistar rats, the proportion of intact mitochondria increased. Conclusion: According to our past and present results, the repair of the mitochondrial apparatus by SkQ1 is a promising strategy against AD.

KW - Alzheimer’s disease

KW - Aβ

KW - Mitochondria

KW - Neurodegeneration

KW - OXYS rats

KW - SkQ1

KW - WISTAR

KW - mitochondria

KW - neurodegeneration

KW - BIOMARKERS

KW - A beta

KW - ULTRASTRUCTURE

KW - SENESCENCE

KW - Alzheimer's disease

UR - http://www.scopus.com/inward/record.url?scp=85031731353&partnerID=8YFLogxK

U2 - 10.2174/1567205014666170621111033

DO - 10.2174/1567205014666170621111033

M3 - Article

AN - SCOPUS:85031731353

VL - 14

SP - 1283

EP - 1292

JO - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

IS - 12

ER -