Alzheimer's Disease-Like Pathology in Senescence-Accelerated OXYS Rats can be Partially Retarded with Mitochondria-Targeted Antioxidant SkQ1

Stefanova, Natalia A.; Muraleva, Natalia A.; Vp, Skulachev; Kolosova, N. G.

doi:10.3233/jad-131034

Cited by 68 publications

(66 citation statements)

References 45 publications

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“…26 OXYS rats overproduce AβPP protein by 13 mo of age, and the protein levels remain high subsequently at 23 mo of age. 41 Thus, histopathologically, Aβ accumulates in the hippocampus and cortex of OXYS rats with age ( Fig. 4A-C).…”

Section: The Ad-like Metabolic Pathway In Oxys Ratsmentioning

confidence: 99%

“…Such lesions were not found in young Wistar rats. 41,63,67 Demyelination occurs both during healthy brain aging and in AD, but the magnitude of changes is significantly different. 68 With age, demyelination is detectable in Wistar rats, but in middle-aged and aged animals the number of demyelinating foci is smaller than that in age-matched OXYS rats (Fig.…”

Section: Signs Of Neurodegeneration In Oxys Ratsmentioning

confidence: 99%

“…40,41,43 At the age of 3 mo, OXYS rats exhibit significantly reduced locomotor and exploratory activities in the open field test and increased anxiety in the elevated plus maze test. These impairments progressively increased with age in OXYS rats, compared with Wistar rats.…”

Section: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 99%

“…49 We have shown that young (age 3 mo) and middle-aged (age 12-16 mo) Wistar rats display the same level of spatial learning, whereas learning and memory deficits in OXYS rats became progressively worse between ages 3 and 16 mo, pointing to gradual deterioration of cognitive function. [40][41][42][43] In contrast, OXYS rats demonstrate learning and reference memory deficits in the 8-arm radial maze already at 3 mo of age (data in preparation).…”

Section: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 99%

“…41 The pathophysiological relevance of tau phosphorylation in AD is still a subject of debate. 104 Accumulating evidence indicates that the initiator of the disease process is alterations in the Aβ peptide.…”

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confidence: 99%

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Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

et al. 2014

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Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. in recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. in addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. with age, neurodegenerative changes in the brain of OXYS rats become amplified. we have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMDlike retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD.

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Section: The Ad-like Metabolic Pathway In Oxys Ratsmentioning

confidence: 99%

Section: Signs Of Neurodegeneration In Oxys Ratsmentioning

confidence: 99%

Section: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 99%

Section: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 99%

mentioning

confidence: 99%

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Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

et al. 2014

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Phenoptosis: Programmed Death of an Organism

2018

Apoptosis and Beyond

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Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation

et al. 2015

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Mitochondria, once merely considered as the "powerhouse" of cells, as they generate more than 90 % of cellular ATP, are now known to play a central role in many metabolic processes, including oxidative stress and apoptosis. More than 40 known human diseases are the result of excessive production of reactive oxygen species (ROS), bioenergetic collapse and dysregulated apoptosis. Mitochondria are the main source of ROS in cells, due to the activity of the respiratory chain. In normal physiological conditions, ROS generation is limited by the anti-oxidant enzymatic systems in mitochondria. However, disregulation of the activity of these enzymes or interaction of respiratory complexes with mitochondriotropic agents may lead to a rise in ROS concentrations, resulting in oxidative stress, mitochondrial permeability transition (MPT) induction and triggering of the apoptotic pathway. ROS concentration is also increased by the activity of amine oxidases located inside and outside mitochondria, with oxidation of biogenic amines and polyamines. However, it should also be recalled that, depending on its concentration, the polyamine spermine can also protect against stress caused by ROS scavenging. In higher organisms, cell signaling pathways are the main regulators in energy production, since they act at the level of mitochondrial oxidative phosphorylation and participate in the induction of the MPT. Thus, respiratory complexes, ATP synthase and transition pore components are the targets of tyrosine kinases and phosphatases. Increased ROS may also regulate the tyrosine phosphorylation of target proteins by activating Src kinases or phosphatases, preventing or inducing a number of pathological states.

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Alzheimer's Disease-Like Pathology in Senescence-Accelerated OXYS Rats can be Partially Retarded with Mitochondria-Targeted Antioxidant SkQ1

Cited by 68 publications

References 45 publications

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease

Phenoptosis: Programmed Death of an Organism

Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation

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