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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Wiley
2018-01-01
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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. |
format | Article |
id | doaj-art-9ec0591ead9e4b5bb341cd6918152f8d |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2018-01-01 |
publisher | Wiley |
record_format | Article |
series | Mediators of Inflammation |
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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