Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo

Abstract Several studies indicate that erythropoietin (EPO) has remarkable neuroprotective effects in various central nervous system disorders, while little is known about the effects of EPO in diabetes-associated cognitive dysfunction. Therefore, the present study aimed to investigate whether EPO a...

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Autores principales: Meng Wang, Wenhui Yan, Yuan Liu, Hao Hu, Qiang Sun, Xinlin Chen, Weijin Zang, Lina Chen
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/a5b10f1360684aad8b1da859e2ea4d52
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spelling oai:doaj.org-article:a5b10f1360684aad8b1da859e2ea4d522021-12-02T15:06:17ZErythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo10.1038/s41598-017-03137-62045-2322https://doaj.org/article/a5b10f1360684aad8b1da859e2ea4d522017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03137-6https://doaj.org/toc/2045-2322Abstract Several studies indicate that erythropoietin (EPO) has remarkable neuroprotective effects in various central nervous system disorders, while little is known about the effects of EPO in diabetes-associated cognitive dysfunction. Therefore, the present study aimed to investigate whether EPO ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro. We investigated the protective effects of EPO on high-glucose (HG)-induced PC12 cell death and oxidative stress. The effects of EPO (300 U/kg administered three times a week for 4 weeks) on diabetes-associated cognitive decline were investigated in diabetic rats. EPO significantly increased cell viability, increased the activity of superoxide dismutase, decreased the production of malondialdehyde and reactive oxygen species, and decreased the apoptosis rate. Additionally, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, abolished the protective effects of EPO in HG-treated PC12 cells. In diabetic rats, EPO prevented deficits in spatial learning and memory in the Morris water maze test. The results of real-time PCR and Western blotting showed that EPO upregulated EPO receptor, PI3K, and phosphorylated Akt2 relative to unphosphorylated Akt2 (p-Akt2/Akt2) and downregulated glycogen synthase kinase-3β (GSK-3β). These studies demonstrate that EPO is an effective neuroprotective agent in the context of diabetes-associated cognitive dysfunction and show that this effect involves the PI3K/Akt/GSK-3β pathway.Meng WangWenhui YanYuan LiuHao HuQiang SunXinlin ChenWeijin ZangLina ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Meng Wang
Wenhui Yan
Yuan Liu
Hao Hu
Qiang Sun
Xinlin Chen
Weijin Zang
Lina Chen
Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
description Abstract Several studies indicate that erythropoietin (EPO) has remarkable neuroprotective effects in various central nervous system disorders, while little is known about the effects of EPO in diabetes-associated cognitive dysfunction. Therefore, the present study aimed to investigate whether EPO ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro. We investigated the protective effects of EPO on high-glucose (HG)-induced PC12 cell death and oxidative stress. The effects of EPO (300 U/kg administered three times a week for 4 weeks) on diabetes-associated cognitive decline were investigated in diabetic rats. EPO significantly increased cell viability, increased the activity of superoxide dismutase, decreased the production of malondialdehyde and reactive oxygen species, and decreased the apoptosis rate. Additionally, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, abolished the protective effects of EPO in HG-treated PC12 cells. In diabetic rats, EPO prevented deficits in spatial learning and memory in the Morris water maze test. The results of real-time PCR and Western blotting showed that EPO upregulated EPO receptor, PI3K, and phosphorylated Akt2 relative to unphosphorylated Akt2 (p-Akt2/Akt2) and downregulated glycogen synthase kinase-3β (GSK-3β). These studies demonstrate that EPO is an effective neuroprotective agent in the context of diabetes-associated cognitive dysfunction and show that this effect involves the PI3K/Akt/GSK-3β pathway.
format article
author Meng Wang
Wenhui Yan
Yuan Liu
Hao Hu
Qiang Sun
Xinlin Chen
Weijin Zang
Lina Chen
author_facet Meng Wang
Wenhui Yan
Yuan Liu
Hao Hu
Qiang Sun
Xinlin Chen
Weijin Zang
Lina Chen
author_sort Meng Wang
title Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
title_short Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
title_full Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
title_fullStr Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
title_full_unstemmed Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
title_sort erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivo
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/a5b10f1360684aad8b1da859e2ea4d52
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