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

Abstract

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.

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

“…9 Moreover, SkQ1 increases the aB-crystallin level and decreases the Ab level in the retina (manuscript in preparation) as well as in the brain. 40 These findings are consistent with the present study and support the view that aB-crystallin is involved in degeneration of the retina.…”

“…39 Recently, we showed that Ab accumulates with age in the retina and in the brain of OXYS rats; 22,40 however, the level of Ab is not elevated at the early stages of retinopathy, that is, at the age of 3 months. 22 The Ab level increases in the retina of middle-aged and old OXYS rats, when these rats present with severe stages of the disease accompanied by pronounced neurodegenerative changes.…”

Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease

“…Recently, our group showed that OXYS rats exhibit signs of AD-like pathology; in particular, amyloid-b accumulates in the hippocampus and cortex of OXYS rats with age, although substantial amyloid-b accumulation occurs only at 13 months of age (Stefanova et al 2014a). Thus, in OXYS rats, the alterations of melatonin secretion occur before accumulation of amyloid-b.…”

“…OXYS rats are characterized by progressive age-related aggregation of amyloid-b and hyperphosphorylation of the tau protein as well as mitochondrial dysfunction, loss of synapses, neuronal death, and ultimately cognitive decline (Stefanova et al 2010(Stefanova et al , 2011(Stefanova et al , 2014a. We demonstrated previously that the signs of accelerated aging of the brain in OXYS rats develop simultaneously with changes in the metabolism of the neurotransmitter serotonin in the brain regions that are essential for learning and memory (Shcheglova et al 2002).…”

Racemized and Isomerized Proteins in Aging Rat Teeth and Eye Lens

“…[1][2][3][4] This research often involves transgenic or knockout rodent lines for the analysis of a specific gene, protein, or phenotype. For these studies, it is useful to correlate age, genetic alterations, or therapeutic interventions with changes in molecular markers of aging.…”