Resveratrol improves neuron protection and functional recovery in rat model of spinal cord injury

Liu, Changjiang; Shi, Zhibin; Fan, Lihong; Zhang, Chen; Wang, Kunzheng; Wang, Bo

doi:10.1016/j.brainres.2010.11.061

Cited by 149 publications

(113 citation statements)

References 40 publications

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“…61 In the same line, RSV has been reported to normalize GSH or MDA levels in a rat model of spinal cord injury 62 or in the brain of obese mice. 63 Since the discovery of sirtuin-activating compounds such as RSV, 4 a rich controversy exists regarding the direct path via SIRT1 or via an indirect modus operandi of these compounds.…”

Section: Discussionmentioning

confidence: 89%

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

et al. 2015

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Oxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired. Cell Death and Differentiation (2015) 22, 1742-1753 doi:10.1038/cdd.2015; published online 27 March 2015Sirtuins are highly conserved NAD + -dependent deacetylases with a critical impact on metabolic adaptive responses. In mammals, among the seven members of the sirtuin family (SIRT1-SIRT7), SIRT1 has been the most extensively characterized. 1 SIRT1 promotes the generation of new mitochondria through the activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), which orchestrates the mitochondrial biogenesis program through the transcriptional activation of nuclear respiratory factors (NRF-1 and NRF-2) and mitochondrial transcription factor A (TFAM). 2 SIRT1 activity is finely regulated not only by gene expression and protein levels but also by posttranslational modifications, its oligomeric status, the interaction with the DBC1 and AROS proteins, and the levels of NAD + /NADH/NAM. 3 In addition, SIRT1 activity is modulated by several synthetic or natural molecules such as the polyphenol resveratrol (3,4',5-trihydroxystilbene: RSV). 4 The activation of SIRT1 by transgenic overexpression or pharmacologically with RSV has been shown to prevent the pathology in diseases commonly associated with mitochondrial dysfunction such as the metabolic syndrome and neurodegenerative disorders, 1,5,6 albeit recent findings cast doubts on the universal validity of the results. 7,8 Although prominent axonal pathology often precedes cell body loss in many neurodegenerative diseases, 9 the potential of SIRT1 activation in axonal degeneration has not been addressed in depth. In this work, we take advantage of the cellular and animal models of the rare monogenic neurodegenerative disease named X-linked adrenoleukodystrophy (X-ALD, (McKusick No.300100)) to evaluate the impact of SIRT1 function on axonal degeneration. X-ALD is the most prevalent peroxisomal disorder (minimum incidence 1:17 000 newborns), characterized by brain inflammatory demyelination and/or axonopathy of long tracts in spinal cords, adrenal insufficiency and a pathognomonic accumulation of very longchain fatty acids (VLCFA) in plasma and tissues, in particular hexacosanoic acid (C26:0). 10,11 The disease phenotypes range from adrenal ...

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Section: Discussionmentioning

confidence: 89%

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

et al. 2015

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“…Indeed, potent therapeutic effects of resveratrol administration were reported in animal models of Alzheimer's disease and accelerated ageing [10,26,46], multiple sclerosis [47,48], Huntington's disease [9,49], Parkinson's disease [22,50], and even reducing peripheral axonal degeneration [51] or promoting functional recovery after traumatic spinal cord injury [23]. In this sense, resveratrol has been also reported to exert neuroprotection on in vitro models of ALS.…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol administration has been shown to provide beneficial effects on several neurodegenerative disease models, such as Alzheimer's disease [10] and Parkinson's disease [22] and in traumatic [23] and ischemic injuries to the central nervous system [24]. Since previous studies showed that resveratrol administration protects MN on in vitro ALS models [25,26], the main goal of the present work was to assess the potential therapeutic effect of a resveratrol-enriched diet in the SOD1 G93A mouse model of ALS.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

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Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1 G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests.We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1 G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1 G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

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“…In their study resveratrol crossed the placental barrier and exerted its antioxidant potentials in neonates. Liua et al in their work found that resveratrol can efficiently interrupt the neuronal apoptosis by regulating the expression of apoptosis proteins, thus enhancing recovery of the neurological function [33]. Resveratrol significantly promoted the recovery of rat dorsal neuronal function after spinal cord injury, and this effect is related to its characteristics of anti-oxidation, anti-inflammation and anti-apoptosis.…”

Section: Comparison Of Values Of Bdnf Expression Between Resveratrol mentioning

confidence: 97%

A Comparison of Resveratrol and Vitamin C Therapy on Expression of BDNF in Stressed Rat Brain Homogenate

Ashwin¹

2013

iosrphr

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Resveratrol improves neuron protection and functional recovery in rat model of spinal cord injury

Cited by 149 publications

References 40 publications

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

A Comparison of Resveratrol and Vitamin C Therapy on Expression of BDNF in Stressed Rat Brain Homogenate

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