Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis

Abstract Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes‐induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes‐related cognitive dysfunction...

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Main Authors: Ying Hu, Qin Zhang, Jian‐Cheng Wang, Jiao Wang, Ying Liu, Ling‐Yan Zhu, Ji‐Xiong Xu
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:Kaohsiung Journal of Medical Sciences
Subjects:
Online Access:https://doi.org/10.1002/kjm2.12643
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author Ying Hu
Qin Zhang
Jian‐Cheng Wang
Jiao Wang
Ying Liu
Ling‐Yan Zhu
Ji‐Xiong Xu
author_facet Ying Hu
Qin Zhang
Jian‐Cheng Wang
Jiao Wang
Ying Liu
Ling‐Yan Zhu
Ji‐Xiong Xu
author_sort Ying Hu
collection DOAJ
description Abstract Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes‐induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes‐related cognitive dysfunction in vivo and in vitro. We induced a rat diabetic model with a high‐fat and high‐sucrose diet followed by intraperitoneal injection of streptozotocin and a diabetic neuron cell model by stimulation with high levels of glucose. We observed that RSV improved impairment in spatial learning and memory in the Morris water maze test (MWM) and novel object recognition test (ORT) in diabetic rats. RSV reversed the reduced miR‐146a‐5p and upregulated thioredoxin‐interacting protein (TXNIP) and inhibited the diabetes‐induced increase in interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α levels in vivo and in vitro. RSV also inhibited diabetes‐induced endoplasmic reticulum stress (ESR) by reducing ESR‐related protein expression in vivo and in vitro. Moreover, inhibition of miR‐146a‐5p partially abolished the protective effects of RSV in HG‐treated primary neurons. Additionally, we used starBase to predict that miR‐146a‐5p interacts with TXNIP, which we then verified using a luciferase reporter gene assay. We further observed that miR‐146a‐5p regulates the mRNA and protein expression of TXNIP in vitro, indicating that the miR‐146a‐5p/TXNIP axis is involved in the regulation of cognitive dysfunction in a rat diabetic model. Collectively, these results demonstrate that RSV plays a neuroprotective role in diabetes‐associated cognitive dysfunction at least in part through regulation of the miR‐146a‐5p/TXNIP axis.
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spelling doaj.art-da785cf1a946484994319ed4c50013cd2023-04-10T06:31:28ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-04-0139440441510.1002/kjm2.12643Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axisYing Hu0Qin Zhang1Jian‐Cheng Wang2Jiao Wang3Ying Liu4Ling‐Yan Zhu5Ji‐Xiong Xu6Department of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaDepartment of Anesthesiology and Operative Medicine, Medical Center of Anesthesiology and Pain Nanchang People's Republic of ChinaDepartment of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaDepartment of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaDepartment of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaDepartment of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaDepartment of Endocrinology and Metabolism First Affiliated Hospital of Nanchang University Nanchang People's Republic of ChinaAbstract Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes‐induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes‐related cognitive dysfunction in vivo and in vitro. We induced a rat diabetic model with a high‐fat and high‐sucrose diet followed by intraperitoneal injection of streptozotocin and a diabetic neuron cell model by stimulation with high levels of glucose. We observed that RSV improved impairment in spatial learning and memory in the Morris water maze test (MWM) and novel object recognition test (ORT) in diabetic rats. RSV reversed the reduced miR‐146a‐5p and upregulated thioredoxin‐interacting protein (TXNIP) and inhibited the diabetes‐induced increase in interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α levels in vivo and in vitro. RSV also inhibited diabetes‐induced endoplasmic reticulum stress (ESR) by reducing ESR‐related protein expression in vivo and in vitro. Moreover, inhibition of miR‐146a‐5p partially abolished the protective effects of RSV in HG‐treated primary neurons. Additionally, we used starBase to predict that miR‐146a‐5p interacts with TXNIP, which we then verified using a luciferase reporter gene assay. We further observed that miR‐146a‐5p regulates the mRNA and protein expression of TXNIP in vitro, indicating that the miR‐146a‐5p/TXNIP axis is involved in the regulation of cognitive dysfunction in a rat diabetic model. Collectively, these results demonstrate that RSV plays a neuroprotective role in diabetes‐associated cognitive dysfunction at least in part through regulation of the miR‐146a‐5p/TXNIP axis.https://doi.org/10.1002/kjm2.12643diabetes‐induced cognitive dysfunctionmiR‐146a‐5presveratrolTXNIP
spellingShingle Ying Hu
Qin Zhang
Jian‐Cheng Wang
Jiao Wang
Ying Liu
Ling‐Yan Zhu
Ji‐Xiong Xu
Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
Kaohsiung Journal of Medical Sciences
diabetes‐induced cognitive dysfunction
miR‐146a‐5p
resveratrol
TXNIP
title Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
title_full Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
title_fullStr Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
title_full_unstemmed Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
title_short Resveratrol improves diabetes‐induced cognitive dysfunction in part through the miR‐146a‐5p/TXNIP axis
title_sort resveratrol improves diabetes induced cognitive dysfunction in part through the mir 146a 5p txnip axis
topic diabetes‐induced cognitive dysfunction
miR‐146a‐5p
resveratrol
TXNIP
url https://doi.org/10.1002/kjm2.12643
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