Evaluation of Effects of Histochrome and Mexidol on Structural and Functional Characteristics of the Brain in Senescence-Accelerated OXYS Rats by Magnetic Resonance Imaging

Агафонова, И. Г.; Kotelnikov, V. N.; Mischenko, Natalia P.; Kolosova, N. G.

doi:10.1007/s10517-011-1238-7

Cited by 17 publications

(9 citation statements)

References 5 publications

(6 reference statements)

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“…In animal models of neurodegenerative diseases including AD, neuroprotective and neuroregenerative mechanisms of EPO are related to inhibiting apoptosis, reducing oxidative stress and inflammation, promoting the angiogenesis and neurogenesis, and maintaining blood brain barrier (BBB) integrity [ 31 ]. The latter effect might be especially important mechanism in OXYS model due to neurovascular disturbances registered in OXYS rats [ 10 , 32 , 33 ]. Moreover, recent evidence suggests that cerebrovascular degeneration contributes to the pathogenesis of AD by causing faulty clearance of Aβ across the BBB [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties

et al. 2018

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Background The dominant hypothesis about the pathogenesis of Alzheimer’s disease (AD) is the “amyloid cascade” concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD. The molecular mechanisms of this effect are not completely clear, we suggested that the drug might serve as the regulator of the expression of the genes involved in the metabolism of Aβ and the pathogenesis of AD. The study was aimed to determine the effects of CEF on mRNA levels of Bace1 (encoding β-secretase BACE1 involved in Aβ production), Mme, Ide, Ece1, Ace2 (encoding enzymes involved in Aβ degradation), Epo (encoding erythropoietin related to endothelial function and clearance of Aβ across the blood brain barrier) in the frontal cortex, hippocampus, striatum, hypothalamus, and amygdala of OXYS and Wistar (control strain) male rats. Starting from the age of 14 weeks, animals received CEF (100 mg/kg/day, i.p., 36 days) or saline. mRNA levels were evaluated with RT-qPCR method. Biochemical parameters of plasma were measured for control of system effects of the treatment.ResultsTo better understand strain variations studied here, we compared the gene expression between untreated OXYS and Wistar rats. This comparison showed a significant decrease in mRNA levels of Ace2 in the frontal cortex and hypothalamus, and of Actb in the amygdala of untreated OXYS rats. Analysis of potential effects of CEF revealed its novel targets. In the compound-treated OXYS cohort, CEF diminished mRNA levels of Bace1 and Ace2 in the hypothalamus, and Aktb in the frontal cortex. Furthermore, CEF augmented Mme, Ide, and Epo mRNA levels in the amygdala as well as the levels of Ece1 and Aktb in the striatum. Finally, CEF also attenuated the activity of ALT and AST in plasma of OXYS rats.ConclusionThose findings disclosed novel targets for CEF action that might be involved into neuroprotective mechanisms at early, pre-plaque stages of AD-like pathology development.

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Section: Discussionmentioning

confidence: 99%

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties

et al. 2018

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“…61 With age, the adaptive resources of OXYS rats decline. Examination of cerebral vessels and parameters of cerebral blood flow on MRI (in 12-mo-old OXYS rats) revealed structural and functional changes, including reduced reactivity of vessels typical for chronic ischemia, 62,63 a condition that inevitably contributes to the progression of neurodegenerative changes. Chronic ischemia induced by diffuse insufficiency of blood supply to the brain leads to deterioration of brain function and to the development of cognitive and behavioral deficits in elderly people.…”

Section: Signs Of Neurodegeneration 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%

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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“…The behavior of young OXYS and old Wistar rats are similar. In OXYS rats, the behavioral alterations develop by the age of 3 months, preceded by progressive signs of neuro-degeneration (detected by magnetic resonance imaging, MRI) [ 36 - 39 ]. Another manifestation of the accelerated brain aging of OXYS rats is a decline in the ability of synapses to express plasticity and long-term potentiation (LTP) [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

Kolosova

Vitovtov

Muraleva

et al. 2013

Aging

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Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span in C elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wistar rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

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Evaluation of Effects of Histochrome and Mexidol on Structural and Functional Characteristics of the Brain in Senescence-Accelerated OXYS Rats by Magnetic Resonance Imaging

Cited by 17 publications

References 5 publications

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties

Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties

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

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

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