Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

Tian, Zhiyan; Wang, Jinhua; Xu, Ming; Yan, Wei; Zhang, Miao; Zhou, Yuying

doi:10.1159/000453216

Cited by 56 publications

(33 citation statements)

References 25 publications

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“…The present study provided evidence that resveratrol protects against diabetic cardiomyopathy by activating AMPK and JNK1 pathway to modulate the switch between autophagy and apoptotic machinery. Our results are supported by previous studies that autophagy is suppressed in type 2 diabetes and resveratrol acts as an regulator of autophagy [8, 13] and apoptosis [26]. …”

Section: Discussionsupporting

confidence: 92%

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetic cardiomyopathy is associated with increased apoptosis and suppressed autophagy in cardiac cells. The polyphenol resveratrol has shown beneficial effects in various cardiovascular diseases. This study investigated if resveratrol protected cardiac cells by modulating apoptosis and autophagy in the context of diabetes. Methods: H9c2 cardiac myoblast cells were exposed to high glucose combined with palmitate. Autophagy was evaluated by estimating LC3-II/I ratio, P62 protein levels, and LC3 fluorescent puncta. Apoptosis was assessed by using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), flow cytometry, and analysis of the protein expression of apoptotic markers (cleavage of caspase-3 and PARP). Results: High glucose and palmitate suppressed autophagic activity and exacerbated apoptotic cell death in cardiac myoblast cells. Resveratrol restored autophagy and attenuated apoptosis in cells upon diabetic stimuli. Moreover, resveratrol activated AMPK and JNK1, thereby suppressing mTOR and its downstream effectors p70S6K1 and 4EBP1, as well as disrupting the Beclin1–Bcl-2 complex. Conclusion: Resveratrol protects cardiac cells by regulating the switch between autophagy and apoptotic machinery under diabetic conditions, which is attributed by AMPK-mediated phosphorylation of mTORC1/p70S6K1/4EBP1 and JNK-mediated dissociation of Beclin1-Bcl-2. Our study suggests that autophagy may be an important target for resveratrol in the treatment of diabetic cardiomyopathy.

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Section: Discussionsupporting

confidence: 92%

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

Liu

et al. 2018

Cell Physiol Biochem

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“…A recent study asserted that DM and subarachnoid hemorrhage could occur as a result of the apoptosis of hippocampal neurons, accompanied by increased expressions of caspase‐3, Bax, and Bcl‐2 (He, Sun, & Huang, ). Another study also has found that resveratrol has protective effect on STZ‐induced DM, which may result from inhibiting hippocampal neuron apoptosis via the Bcl‐2, Bax, and caspase‐3 signaling pathways (Z. Tian et al, ). Furthermore, lncRNAs are closely associated with some cellular stress responses such as OS, nutritional deficiency, and DNA damage (Zeng et al, ).…”

Section: Discussionmentioning

confidence: 98%

Retracted: Downregulation of long noncoding RNA H19 rescues hippocampal neurons from apoptosis and oxidative stress by inhibiting IGF2 methylation in mice with streptozotocin‐induced diabetes mellitus

Che

et al. 2018

Journal Cellular Physiology

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The diabetes mellitus (DM)‐induced reduction of neurogenesis in the hippocampus is consequently accompanied by cognitive decline. The present study set out to define the critical role played by long noncoding RNA H19 (lncRNA H19) in the apoptosis of hippocampal neurons, as well as oxidative stress (OS) in streptozotocin (STZ)‐induced DM mice through regulation of insulin‐like growth factor 2 (IGF2) methylation. The expression of lncRNA H19 in the hippocampal neurons and surviving neurons were detected. Hippocampal neurons were cultured and transfected with oe‐H19, sh‐H19, oe‐IGF2, or sh‐IGF2, followed by detection of the expressions of IGF2 and apoptosis‐related genes. Determination of the lipid peroxide and glutathione levels was conducted, while antioxidant enzyme activity was identified. The IGF2 methylation, the binding of lncRNA H19 to DNA methyltransferase, and the binding of lncRNA H19 to IGF2 promoter region were detected. DM mice exhibited high expressions of H19, as well as a decreased hippocampal neurons survival rate. Higher lncRNA H19 expression was found in DM. Upregulated lncRNA H19 significantly increased the expression of Bax and caspase‐3 but decreased that of Bcl‐2, thus promoting the apoptosis of hippocampal neuron. Besides, upregulation of lncRNA H19 induced OS. LncRNA H19 was observed to bind specifically to the IGF2 gene promoter region and promote IGF2 methylation by enriching DNA methyltransferase, thereby silencing IGF2 expression. Taken together, downregulated lncRNA H19 reduces IGF2 methylation and enhances its expression, thereby suppressing hippocampal neuron apoptosis and OS in STZ‐induced (DM) mice.

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“…Of these, the fact that phosphorylation levels of SIRT1 and AMPK in Pb-exposed mice were restored by resveratrol treatment reflected the action of resveratrol on SIRT1/AMPK activation. Moreover, it is reported that resveratrol can promote SIRT1/AMPK activation (Valenti et al, 2016) and is implicated in neural plasticity (Torres-Pérez et al, 2015; Dias et al, 2016; Tian et al, 2016). Similar to our results for pSIRT1, the present study showed probe time in target area of the MWM test was also positively correlated with the ratio of pAMPK/AMPK which enhanced the link between cognition and resveratrol involving AMPK.…”

Section: Discussionmentioning

confidence: 99%

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

Zhang

Wang

et al. 2017

Front. Physiol.

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Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac)2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ1−−40. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.

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Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

Cited by 56 publications

References 25 publications

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

Resveratrol Modulates Apoptosis and Autophagy Induced by High Glucose and Palmitate in Cardiac Cells

Retracted: Downregulation of long noncoding RNA H19 rescues hippocampal neurons from apoptosis and oxidative stress by inhibiting IGF2 methylation in mice with streptozotocin‐induced diabetes mellitus

Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

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