Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes

Neurons suffer detrimental effects from β-amyloid toxicity in Alzheimer’s disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons agai...

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Main Authors: Kexin Wang, Hongyan Li, Hongxing Wang, Jun-hui Wang, Feng Song, Yu Sun
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/9070341
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author Kexin Wang
Hongyan Li
Hongxing Wang
Jun-hui Wang
Feng Song
Yu Sun
author_facet Kexin Wang
Hongyan Li
Hongxing Wang
Jun-hui Wang
Feng Song
Yu Sun
author_sort Kexin Wang
collection DOAJ
description Neurons suffer detrimental effects from β-amyloid toxicity in Alzheimer’s disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons against the Aβ-induced cell toxicity so far. In the present study, we investigated whether irisin could protect neurons against Aβ- (25–35) induced cell damage and explored the possible underlying mechanisms. Primary cell cultures of astrocytes and neurons were established. Conditioned medium from astrocyte was collected for the treatment and biochemistry assay study. To explore the protein expression changes, Western blot and ELISA assays were used in these in vitro cell culture models. Exposure of hippocampal neurons to 10 μM Aβ (25–35) caused significant reduction on cell viability, and the toxic effect was not significantly reduced by the coadministration of irisin. However, pretreated astrocyte-conditioned medium with irisin for 12 hours notably protected the neurons from the toxicity of Aβ. Also, we found that irisin could attenuate the release of IL-6 and IL-1β from cultured astrocytes and decrease the expression level of COX-2 and phosphorylation of AKT. Last, we found that irisin could reduce NFκB activation in astrocyte exposed to Aβ by preventing the phosphorylation and the loss of IκBα. Our finding may provide novel evidence for the future application of irisin in the treatment of Alzheimer’s disease and the memory dysfunction in diabetes mellitus.
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spelling doaj-art-9ec0591ead9e4b5bb341cd6918152f8d2025-02-03T01:07:02ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/90703419070341Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating AstrocytesKexin Wang0Hongyan Li1Hongxing Wang2Jun-hui Wang3Feng Song4Yu Sun5Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Obstetrics and Gynecology, The Eighth People’s Hospital of Qingdao, Qingdao, Shandong, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Physiology, University of Toronto, Toronto, Ontario, CanadaDepartment of Orthopedics, Qingdao University Affiliated Qingdao Municipal Hospital, Qingdao, Shandong, ChinaDepartment of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaNeurons suffer detrimental effects from β-amyloid toxicity in Alzheimer’s disease. The exercise hormone, irisin, is found to induce a neuroprotective gene program and facilitates the beneficial effects on cognitive function. But no effort is made to test its direct protective effects on neurons against the Aβ-induced cell toxicity so far. In the present study, we investigated whether irisin could protect neurons against Aβ- (25–35) induced cell damage and explored the possible underlying mechanisms. Primary cell cultures of astrocytes and neurons were established. Conditioned medium from astrocyte was collected for the treatment and biochemistry assay study. To explore the protein expression changes, Western blot and ELISA assays were used in these in vitro cell culture models. Exposure of hippocampal neurons to 10 μM Aβ (25–35) caused significant reduction on cell viability, and the toxic effect was not significantly reduced by the coadministration of irisin. However, pretreated astrocyte-conditioned medium with irisin for 12 hours notably protected the neurons from the toxicity of Aβ. Also, we found that irisin could attenuate the release of IL-6 and IL-1β from cultured astrocytes and decrease the expression level of COX-2 and phosphorylation of AKT. Last, we found that irisin could reduce NFκB activation in astrocyte exposed to Aβ by preventing the phosphorylation and the loss of IκBα. Our finding may provide novel evidence for the future application of irisin in the treatment of Alzheimer’s disease and the memory dysfunction in diabetes mellitus.http://dx.doi.org/10.1155/2018/9070341
spellingShingle Kexin Wang
Hongyan Li
Hongxing Wang
Jun-hui Wang
Feng Song
Yu Sun
Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
Mediators of Inflammation
title Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
title_full Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
title_fullStr Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
title_full_unstemmed Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
title_short Irisin Exerts Neuroprotective Effects on Cultured Neurons by Regulating Astrocytes
title_sort irisin exerts neuroprotective effects on cultured neurons by regulating astrocytes
url http://dx.doi.org/10.1155/2018/9070341
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AT hongxingwang irisinexertsneuroprotectiveeffectsonculturedneuronsbyregulatingastrocytes
AT junhuiwang irisinexertsneuroprotectiveeffectsonculturedneuronsbyregulatingastrocytes
AT fengsong irisinexertsneuroprotectiveeffectsonculturedneuronsbyregulatingastrocytes
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