Effects of Cistanche deserticola on behavior and signs of cataract and retinopathy in senescence-accelerated OXYS rats

Stefanova, Natalia A.; Фурсова, А. Ж.; Sarsenbaev, Kanat N.; Kolosova, N. G.

doi:10.1016/j.jep.2011.10.017

Cited by 30 publications

(25 citation statements)

References 55 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the age of 12 and 24 months, OXYS rats had the highest level of Aβ 1–42 in both the hippocampus and cortex compared to Wistar rats ( p < 0.05; Table 1) but not at 3 months of age ( p > 0.05). Note that at this age, OXYS rats show significant behavioral abnormalities and a cognitive decline [7, 8, 10, 11]. The levels of Aβ 1–40 in the cortex and hippocampus were affected by age (F 2,42 = 19.0, p = 0.001, and F 2,42 = 85.1, p = 0.001, respectively) and genotype (only in the hippocampus: F 1,42 = 4.5, p = 0.045).…”

Section: Resultsmentioning

confidence: 99%

“…It seems that these factors are involved in significant structural changes of neurons in 4-month-old OXYS rats, with an increase in the number of dead or damaged neurons by the age of 18 months. The dysfunctional neurogenesis in the hippocampus and cortex leads to subtle early manifestations of the disease, which could in turn render neurons more vulnerable to AD-like pathology and contribute to memory impairment [10, 11]. …”

Section: Discussionmentioning

confidence: 99%

“…Major functions of mitochondria in neurons include regulation of Ca 2+ and redox signaling, developmental and synaptic plasticity, and arbitration of cell survival and death [13]. The age-associated cognitive decline in OXYS rats, particularly impairment of spatial learning [10–11], is associated with changes in the hippocampal synaptic plasticity including a deficit in long-term potentiation starting at 3–4 months of age [38]. Plasticity, the process through which synapses modulate their strength and neurons form new connections, performs a particularly important function in the response to injury and disease, including AD [27].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

et al. 2014

Self Cite

View full text Add to dashboard Cite

The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer's disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ1–42 and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…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%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2014

Self Cite

View full text Add to dashboard Cite

Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-β accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology.

show abstract

Effects of Cistanche deserticola on behavior and signs of cataract and retinopathy in senescence-accelerated OXYS rats

Cited by 30 publications

References 55 publications

Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

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

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

Contact Info

Product

Resources

About