Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats

Kolosova, N. G.; Shcheglova, Tatiana; Sergeeva, Svetlana V.; Loskutova, L. V.

doi:10.1016/j.neurobiolaging.2005.07.022

Cited by 97 publications

(60 citation statements)

References 34 publications

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“…These deficits progressively worsened with age. 48 In the Morris water maze, the old rats show reduced spatial memory compared with young rats, while young and middleaged animals do not differ from each other. 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.…”

Section: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 97%

“…On the other hand, our research into oxidative stress markers in OXYS rats has demonstrated that accumulation as well as imbalance of these markers in redox regulation appears later than the main manifestations of accelerated senescence. 48,77,78 Higher superoxide dismutase (SOD) activity and a decreased level of reduced glutathione in the brain of young OXYS rats indicate effective functioning of the antioxidant system: probably the result of increased production of free radicals. SOD activity is affected by reactive oxygen species and can increase in response to oxidative stress; therefore, one could say that the observed increase in SOD activity in the brain of young OXYS rats reflects either the adaptation to more rapid oxidative metabolism or increased generation of reactive oxygen species (ROS) in the brain of OXYS rats.…”

Section: Oxidative Stress and Mitochondrial Dysfunction In Oxys Ratsmentioning

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: Behavioral Impairments and Learning Deficits In Oxys Ratsmentioning

confidence: 97%

Section: Oxidative Stress and Mitochondrial Dysfunction In Oxys Ratsmentioning

confidence: 99%

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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“…Not surprising therefore that anti-oxidants were intensively tested as potential therapeutic agents against the negative consequences of brain ageing and neurodegenerative disorders [84][85][86]. Generally, it was found that anti-oxidant treatment or activation of anti-oxidative pathways improve brain functions and partially restores age-dependent changes in gene expression both in normal ageing [87,88] and in models of accelerated ageing [89,90]. Clinical data suggest that dietary anti-oxidants have some protective effects against AD, Parkinson's disease and amyotrophic lateral sclerosis [91] and also in pharmacological and genetic models of neurodegenerative disorders [92][93][94].…”

Section: Processes Contributing To Brain Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

114

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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“…In addition, OXYS rats show an early development of ageassociated pathological phenotypes similar to several geriatric disorders observed in humans, including cataract and retinopathy [16,17]. It was hypothesized that the accelerated senescence of OXYS rats is also associated with progressive mitochondrial dysfunction and, indeed, dietary supplementation with antioxidants can prevent the premature deterioration of mitochondrial function typical of OXYS rats [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

Stefanova

Фурсова

Kolosova

2010

JAD

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Abstract. Mitochondrial dysfunction is involved in aging and in neurodegenerative diseases and, therefore, pharmacological agents that alleviate mitochondrial dysfunction are expected to have neuroprotective effects. Promising in this respect is mitochondrial-targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1). We investigated the effects of SkQ1 (250 nmol SkQ1/kg × day with food) on behavior in the elevated plus-maze (EPM) and open field (OF) and on spatial memory in a Morris water maze (MWM) in middle-aged (12 mo) Wistar and senescence-accelerated OXYS rats. Given that changes in the behavior of OXYS rats may be associated with visual impairment, the condition of the retina and the lens was evaluated by ophthalmoscopy. 14-month-old as well as 3-month-old OXYS rats had considerably reduced activities in OF, increased anxiety in EPM, and manifested impaired learning abilities in the MWM in comparison with Wistar rats. SkQ1-treated rats of both strains displayed significantly higher locomotor and exploratory activity in the OF and less anxiety in the EPM compared to age-matched controls. SkQ1 significantly improved visual ability of the rats reducing the severity of the developed signs of retinopathy and cataract but had no impact on OXYS rat's spatial memory in the MWM. SkQ1-treated Wistar rats exhibited slower learning in the MWM task comparison to the control group. Thus, SkQ1 had beneficial effects on locomotor and exploratory functions of the rat brain. Nevertheless, SkQ1 did not alter learning performance in the MWM in OXYS rats and slightly reduced it in the Wistar strain, which may be associated with differences in redox homeostasis.

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Long-term antioxidant supplementation attenuates oxidative stress markers and cognitive deficits in senescent-accelerated OXYS rats

Cited by 97 publications

References 34 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

The endocannabinoid system in normal and pathological brain ageing

Behavioral Effects Induced by Mitochondria-Targeted Antioxidant SkQ1 in Wistar and Senescence-Accelerated OXYS Rats

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