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

Autor: Facai Wang, Yuxian Shen, Shengyun Fang, Yujun Shen, Da-Qin Cha, Lijie Feng, Aimin Sun, Haiping Wang, Yunhong Wang
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
medicine.medical_specialty
Time Factors
Immunology
Ciliary neurotrophic factor
lcsh:RC346-429
Rats
Sprague-Dawley

Cellular and Molecular Neuroscience
Pregnancy
Neurotrophic factors
Internal medicine
Glial Fibrillary Acidic Protein
medicine
Glial cell line-derived neurotrophic factor
Animals
Nerve Growth Factors
Enzyme Inhibitors
Glial activation
Hypoxia
Cells
Cultured

lcsh:Neurology. Diseases of the nervous system
Neurons
biology
Glial fibrillary acidic protein
Microglia
Research
General Neuroscience
Brain
Infarction
Middle Cerebral Artery

Cerebral ischemia
Embryo
Mammalian

Cyclic Nucleotide Phosphodiesterases
Type 3

Rats
Cell biology
Disease Models
Animal

Glucose
medicine.anatomical_structure
Endocrinology
Nerve growth factor
Gene Expression Regulation
Neurology
Mesencephalic astrocyte-derived neurotrophic factor
biology.protein
Endoplasmic reticulum stress
Neuroglia
Female
Propidium
Astrocyte
Zdroj: Journal of Neuroinflammation, Vol 9, Iss 1, p 254 (2012)
Journal of Neuroinflammation
ISSN: 1742-2094
Popis: 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.
Databáze: OpenAIRE