Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

<p>Abstract</p> <p>Background</p> <p>Mesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic...

Full description

Bibliographic Details
Main Authors: Shen Yujun, Sun Aimin, Wang Yunhong, Cha Daqin, Wang Haiping, Wang Facai, Feng Lijie, Fang Shengyun, Shen Yuxian
Format: Article
Language:English
Published: BMC 2012-11-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://www.jneuroinflammation.com/content/9/1/254
_version_ 1828438093158416384
author Shen Yujun
Sun Aimin
Wang Yunhong
Cha Daqin
Wang Haiping
Wang Facai
Feng Lijie
Fang Shengyun
Shen Yuxian
author_facet Shen Yujun
Sun Aimin
Wang Yunhong
Cha Daqin
Wang Haiping
Wang Facai
Feng Lijie
Fang Shengyun
Shen Yuxian
author_sort Shen Yujun
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Mesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons <it>in vivo</it> or <it>in vitro</it>. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear.</p> <p>Methods</p> <p>The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins.</p> <p>Results</p> <p>We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78.</p> <p>Conclusions</p> <p>These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.</p>
first_indexed 2024-12-10T19:58:03Z
format Article
id doaj.art-977b18150cfb4a7783f508635bb14290
institution Directory Open Access Journal
issn 1742-2094
language English
last_indexed 2024-12-10T19:58:03Z
publishDate 2012-11-01
publisher BMC
record_format Article
series Journal of Neuroinflammation
spelling doaj.art-977b18150cfb4a7783f508635bb142902022-12-22T01:35:36ZengBMCJournal of Neuroinflammation1742-20942012-11-019125410.1186/1742-2094-9-254Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activationShen YujunSun AiminWang YunhongCha DaqinWang HaipingWang FacaiFeng LijieFang ShengyunShen Yuxian<p>Abstract</p> <p>Background</p> <p>Mesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons <it>in vivo</it> or <it>in vitro</it>. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear.</p> <p>Methods</p> <p>The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins.</p> <p>Results</p> <p>We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78.</p> <p>Conclusions</p> <p>These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.</p>http://www.jneuroinflammation.com/content/9/1/254Mesencephalic astrocyte-derived neurotrophic factorEndoplasmic reticulum stressGlial activationCerebral ischemia
spellingShingle Shen Yujun
Sun Aimin
Wang Yunhong
Cha Daqin
Wang Haiping
Wang Facai
Feng Lijie
Fang Shengyun
Shen Yuxian
Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
Journal of Neuroinflammation
Mesencephalic astrocyte-derived neurotrophic factor
Endoplasmic reticulum stress
Glial activation
Cerebral ischemia
title Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
title_full Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
title_fullStr Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
title_full_unstemmed Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
title_short Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation
title_sort upregulation of mesencephalic astrocyte derived neurotrophic factor in glial cells is associated with ischemia induced glial activation
topic Mesencephalic astrocyte-derived neurotrophic factor
Endoplasmic reticulum stress
Glial activation
Cerebral ischemia
url http://www.jneuroinflammation.com/content/9/1/254
work_keys_str_mv AT shenyujun upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT sunaimin upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT wangyunhong upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT chadaqin upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT wanghaiping upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT wangfacai upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT fenglijie upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT fangshengyun upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation
AT shenyuxian upregulationofmesencephalicastrocytederivedneurotrophicfactoringlialcellsisassociatedwithischemiainducedglialactivation