Open Access Highly Accessed Open Badges Research

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

Yujun Shen1, Aimin Sun1, Yunhong Wang1, Daqin Cha1, Haiping Wang12, Facai Wang1, Lijie Feng12, Shengyun Fang1234* and Yuxian Shen12*

Author Affiliations

1 Biopharmaceutical Research Institute, Hefei 230032, P R China

2 School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, P R China

3 Center for Biomedical Engineering and Technology, Baltimore, MD, 21201, USA

4 Department of Physiology, University of Maryland School of Medicine, 725 W Lombard St, Baltimore, MD, 21201, USA

For all author emails, please log on.

Journal of Neuroinflammation 2012, 9:254  doi:10.1186/1742-2094-9-254

Published: 23 November 2012



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.


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.


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.


These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

Mesencephalic astrocyte-derived neurotrophic factor; Endoplasmic reticulum stress; Glial activation; Cerebral ischemia