The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system

Baltanás, Ana; Solesio, María E.; Zalba, Guillermo; Galindo, Marı́a F.; Fortuño, Ana; Jordán, Joaquı́n

doi:10.1007/s13105-013-0271-6

Cited by 24 publications

(20 citation statements)

References 36 publications

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“…Incidentally, the serum levels found in the SAMP8 mice were always lower, independently of the treatment method. We may speculate that senescence alterations reported in SAMP8 kidney and liver may influence hPi metabolism (Baltanás et al, 2013;Bayram et al, 2013). However, this aspect is out of the scope of this work.…”

Section: Serum and Hippocampus Proinsulin Levelsmentioning

confidence: 82%

Proinsulin protects against age-related cognitive loss through anti-inflammatory convergent pathways

et al. 2017

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Brain inflammaging is increasingly considered as contributing to age-related cognitive loss and neurodegeneration. Despite intensive research in multiple models, no clinically effective pharmacological treatment has been found yet. Here, in the mouse model of brain senescence SAMP8, we tested the effects of proinsulin, a promising neuroprotective agent that was previously proven to be effective in mouse models of retinal neurodegeneration. Proinsulin is the precursor of the hormone insulin but also upholds developmental physiological effects, particularly as a survival factor for neural cells. Adeno-associated viral vectors of serotype 1 bearing the human proinsulin gene were administered intramuscularly to obtain a sustained release of proinsulin into the blood stream, which was able to reach the target area of the hippocampus. SAMP8 mice and the control strain SAMR1 were treated at 1 month of age. At 6 months, behavioral testing exhibited cognitive loss in SAMP8 mice treated with the null vector. Remarkably, the cognitive performance achieved in spatial and recognition tasks by SAMP8 mice treated with proinsulin was similar to that of SAMR1 mice. In the hippocampus, proinsulin induced the activation of neuroprotective pathways and the downstream signaling cascade, leading to the decrease of neuroinflammatory markers. Furthermore, the decrease of astrocyte reactivity was a central effect, as demonstrated in the connectome network of changes induced by proinsulin. Therefore, the neuroprotective effects of human proinsulin unveil a new pharmacological potential therapy in the fight against cognitive loss in the elderly.

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Section: Serum and Hippocampus Proinsulin Levelsmentioning

confidence: 82%

Proinsulin protects against age-related cognitive loss through anti-inflammatory convergent pathways

et al. 2017

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“…All these induced a consequent increase in inflammationmediated signals (Calabrese et al, 2011b;Scuto et al, 2019). A few studies have found that oxidative stress (Baltanaś et al, 2013), high levels of inflammation (Ren et al, 2018), activated microglias and astrocytes (Chen et al, 2018) were found in brain tissue of SAMP8 mice, especially the hippocampus. Rb1 and Rg1 were the active ingredients of the root of Panax ginseng C. A. Mayer, which have anti-inflammatory and anti-oxidative stress pharmacological effects (Hui et al, 2017;Xu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Protective Effects of Ginsenosides Rb1 and Rg1 on Improving Cognitive Deficits in SAMP8 Mice Based on Anti-Neuroinflammation Mechanism

Yang

Huang

et al. 2020

Front. Pharmacol.

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This present study was designed to investigate the different effects of ginsenosides Rb1 and Rg1 on improving cognitive deficits in 4-month-old SAMP8 mice. Mice were divided into six groups, including the SAMP8 group, the SAMP8 + Donepezil (1.6 mg/kg) group, the SAMP8 + Rb1 (30 and 60 µmol/kg), and SAMP8 + Rg1 (30 and 60 µmol/kg) groups. SAMR1 mice of the same age were used as the control group. Ginsenosides and donepezil were administrated orally to animals for 8 weeks, then the learning and memory ability of mice were measured by using Morris water maze (MWM) test, object recognition test and passive avoidance experiments. The possible mechanisms were studied including the anti-glial inflammation of Rb1 and Rg1 using HE staining, immunohistochemistry and western blot experiments. Results revealed that Rb1 and Rg1 treatment significantly improved the discrimination index of SAMP8 mice in the object recognition test. Rb1 (60 µmol/kg) and Rg1 (30, 60 µmol/kg) could significantly shorten the escape latency in the acquisition test of the MWM test in SAMP8 mice. Furthermore, Rb1 and Rg1 treatments effectively reduced the number of errors in the passive avoidance task in SAMP8 mice. Western blot experiments revealed that Rb1 showed higher effect than Rg1 in decreasing protein expression levels of ASC, caspase-1 and Ab in the hippocampus of SAMP8 mice, while Rg1 was more effective than Rb1 in decreasing the protein levels of iNOS. In addition, although Rb1 and Rg1 treatments showed significant protective effects in repairing neuronal cells loss and inhibiting the activation of astrocyte and microglia in hippocampus of SAMP8 mice, Rb1 was more effective than Rg1. These results suggest that Rb1 and Rg1 could improve the cognitive impairment in SAMP8 mice, and they have different mechanisms for the treatment of Alzheimer's disease.

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“…In old rats, renal ROS, dysfunction, and structural injury as well as cell senescence markers are increased compared to the young and associated with overexpression of NOX4 and p22phox in the kidney (Simao et al, 2011). The senescence-accelerated mouse prone-8 (SAMP8) shows higher levels of renal NOX2 expression and NADPH oxidase activity at the age of 1 month than the senescence-accelerated-resistant mouse (Baltanas et al, 2013).…”

Section: Common Mechanisms Of Cardiac and Renal Agingmentioning

confidence: 99%

Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly

Toba

Lindsey

2019

Pharmacology & Therapeutics

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Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects. Thus, a comprehensive strategy is needed to evaluate the cardiorenal aging network. Common hallmarks shared across systems include extracellular matrix (ECM) accumulation, along with upregulation of matrix metalloproteinases (MMPs) including MMP-9. The wide range of MMP-9 substrates, including ECM components and inflammatory cytokines, implicates MMP-9 in a variety of pathological and age-related processes. In particular, there is strong evidence that inflammatory cell-derived MMP-9 exacerbates cardiorenal aging. This review explores the potential therapeutic targets against CVD and CKD in the elderly, focusing on ECM and MMP roles.

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The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system

Cited by 24 publications

References 36 publications

Proinsulin protects against age-related cognitive loss through anti-inflammatory convergent pathways

Proinsulin protects against age-related cognitive loss through anti-inflammatory convergent pathways

Comparison of the Protective Effects of Ginsenosides Rb1 and Rg1 on Improving Cognitive Deficits in SAMP8 Mice Based on Anti-Neuroinflammation Mechanism

Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly

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