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Article . 2012
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Journal of Neuroinflammation
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Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

Authors: Shen, Yujun; Sun, Aimin; Wang, Yunhong; Cha, Daqin; Wang, Haiping; Wang, Facai; Feng, Lijie; +2 Authors

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

Abstract

Abstract Background 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 in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods 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. Results 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. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

Subjects by Vocabulary

Microsoft Academic Graph classification: Ciliary neurotrophic factor Neurotrophic factors Glial cell line-derived neurotrophic factor biology Microglia Glial fibrillary acidic protein Cell biology medicine.anatomical_structure Neuroglia Astrocyte medicine.medical_specialty Internal medicine medicine Endocrinology Nerve growth factor biology.protein

Library of Congress Subject Headings: lcsh:RC346-429 lcsh:Neurology. Diseases of the nervous system

Keywords

Male, Time Factors, Rats, Sprague-Dawley, Pregnancy, Enzyme Inhibitors, Glial activation, Hypoxia, Cells, Cultured, Neurons, General Neuroscience, Brain, Infarction, Middle Cerebral Artery, Cerebral ischemia, Neurology, Endoplasmic reticulum stress, Female, Neuroglia, Propidium, Immunology, Cellular and Molecular Neuroscience, Glial Fibrillary Acidic Protein, Animals, Nerve Growth Factors, Research, Embryo, Mammalian, Cyclic Nucleotide Phosphodiesterases, Type 3, Rats, Disease Models, Animal, Glucose, Gene Expression Regulation, Mesencephalic astrocyte-derived neurotrophic factor

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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    67
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
67
Top 10%
Top 10%
Top 10%
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