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      Rehabilitation Training and Resveratrol Improve the Recovery of Neurological and Motor Function in Rats after Cerebral Ischemic Injury through the Sirt1 Signaling Pathway

      research-article
      1 , 1 , 2 , *
      BioMed Research International
      Hindawi Publishing Corporation

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          Abstract

          This study was conducted to investigate the recovery of motor function in rats through the silent information regulator factor 2-related enzyme 1 (Sirt1) signal pathway-mediated rehabilitation training. Middle cerebral artery occlusion (MACO) was used to induce ischemia/reperfusion injury. The rats were subjected to no treatment (model), rehabilitation training (for 21 days), resveratrol (5 mg/kg for 21 days), and rehabilitation training plus resveratrol treatment. 24 h later, They were assessed for neurobehavioral score and motor behavior score and expression of brain derived-nerve neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). Compared with sham group, models had significantly higher neurobehavioral scores, balance beam, and rotary stick scores. Compared with the model group, rats in rehabilitation training and resveratrol groups had significantly reduced scores. Compared with rehabilitation training or resveratrol treatment alone, rehabilitation plus resveratrol further reduced the scores significantly. The percentage of cells expressing BDNF and TrkB and expression levels of BDNF and TrkB were similar between the model and sham groups, significantly increased in rehabilitation training and resveratrol groups, and further increased in rehabilitation training plus resveratrol group. These results indicate that rehabilitation raining plus resveratrol can significantly improve the recovery of motor function in rats after cerebral ischemic injury, which is likely related to the upregulation of the BDNF/TrkB signaling pathway.

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          Most cited references27

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          Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets.

          Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report that overexpression of sirtuin 1 (Sirt1), a mediator of the beneficial metabolic effects of calorie restriction, protects neurons against mutant HTT toxicity, whereas reduction of Sirt1 exacerbates mutant HTT toxicity. Overexpression of Sirt1 improves motor function, reduces brain atrophy and attenuates mutant-HTT-mediated metabolic abnormalities in Huntington's disease mice. Further mechanistic studies suggested that Sirt1 prevents the mutant-HTT-induced decline in brain-derived neurotrophic factor (BDNF) concentrations and the signaling of its receptor, TrkB, and restores dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) concentrations in the striatum. Sirt1 deacetylase activity is required for Sirt1-mediated neuroprotection in Huntington's disease cell models. Notably, we show that mutant HTT interacts with Sirt1 and inhibits Sirt1 deacetylase activity, which results in hyperacetylation of Sirt1 substrates such as forkhead box O3A (Foxo3a), thereby inhibiting its pro-survival function. Overexpression of Sirt1 counteracts the mutant-HTT-induced deacetylase deficit, enhances the deacetylation of Foxo3a and facilitates cell survival. These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease.
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            Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway.

            Many studies have demonstrated that apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Neuroprotective effect of quercetin has been shown in a variety of brain injury models including ischemia/reperfusion. It is not clear whether BDNF-TrkB-PI3K/Akt signaling pathway mediates the neuroprotection of quercetin, though there has been some reports on the quercetin increased brain-derived neurotrophic factor (BDNF) level in brain injury models. We therefore first examined the neurological function, infarct volume and cell apoptosis in quercetin treated middle cerebral artery occlusion (MCAO) rats. Then the protein expression of BDNF, cleaved caspase-3 and p-Akt were evaluated in either the absence or presence of PI3K inhibitor (LY294002) or tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) by immunohistochemistry staining and western blotting. Quercetin significantly improved neurological function, while it decreased the infarct volume and the number of TdT mediated dUTP nick end labeling positive cells in MCAO rats. The protein expression of BDNF, TrkB and p-Akt also increased in the quercetin treated rats. However, treatment with LY294002 or K252a reversed the quercetin-induced increase of BDNF and p-Akt proteins and decrease of cleaved caspase-3 protein in focal cerebral ischemia rats. These results demonstrate that quercetin can decrease cell apoptosis in the focal cerebral ischemia rat brain and the mechanism may be related to the activation of BDNF-TrkB-PI3K/Akt signaling pathway.
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              SIRT1 and AMPK in regulating mammalian senescence: a critical review and a working model.

              Ageing in mammals remains an unsolved mystery. Anti-ageing is a recurring topic in the history of scientific research. Lifespan extension evoked by Sir2 protein in lower organisms has attracted a large amount of interests in the last decade. This review summarizes recent evidence supporting the role of a Sir2 mammalian homologue, SIRT1 (Silent information regulator T1), in regulating ageing and cellular senescence. The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed. In particular, a counter-balancing model involving the cross-talks between SIRT1 and AMP-activated protein kinase (AMPK), another stress and energy sensor, is suggested for controlling the senescence program in mammalian cells. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2016
                27 December 2016
                : 2016
                : 1732163
                Affiliations
                1Rehabilitation Department, Linyi People's Hospital, Linyi, China
                2Department of Rehabilitation, Shandong Medical College, Jinan, China
                Author notes

                Academic Editor: Leon Spicer

                Author information
                http://orcid.org/0000-0002-4744-2469
                Article
                10.1155/2016/1732163
                5223001
                28116292
                661ed7ca-09cc-4ac8-b43a-29c2107708be
                Copyright © 2016 Na Shi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 August 2016
                : 15 October 2016
                : 6 November 2016
                Categories
                Research Article

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