Abstract
Cerebral dopamine neurotrophic factor (CDNF), previously known as the conserved dopamine neurotrophic factor, belongs to the evolutionarily conserved CDNF/mesencephalic astrocyte-derived neurotrophic factor MANF family of neurotrophic factors that demonstrate neurotrophic activities in dopaminergic neurons. The function of CDNF during brain ischemia is still not known. MANF is identified as an endoplasmic reticulum (ER) stress protein; however, the role of CDNF in ER stress remains to be fully elucidated. Here, we test the neuroprotective effect of CDNF on middle cerebral artery occlusion (MCAO) rats and neurons and astrocytes treated with oxygen–glucose depletion (OGD). We also investigate the expression of CDNF in cerebral ischemia and in primary neurons treated with ER stress-inducing agents. Our results show that CDNF can significantly reduce infarct volume, reduce apoptotic cells and improve motor function in MCAO rats, while CDNF can increase the cell viability of neurons and astrocytes treated by OGD. The expression of CDNF was upregulated in the peri-infarct tissue at 2 h of ischemia/24 h reperfusion. ER stress inducer can induce CDNF expression in primary cultured neurons. Our data indicate that CDNF has neuroprotective effects on cerebral ischemia and the OGD cell model and the protective mechanism of CDNF may occur through ER stress pathways.
Highlights
Neurotrophic factors (NTFs) are an important group of secreted proteins that promote the survival, growth, and differentiation of neural cells
Rats were pretreated with phosphate buffer saline (PBS) (n = 8) or with 6 μg of Cerebral dopamine neurotrophic factor (CDNF) (n = 10) (Figure 1A)
A significantly smaller infarct volume was observed in the CDNF pretreatment group than in the PBS treatment group after a 24-h reperfusion (8.67 ± 8.45% versus 20.53 ± 9.96%)
Summary
Neurotrophic factors (NTFs) are an important group of secreted proteins that promote the survival, growth, and differentiation of neural cells. At the very end of the C-terminus, the CDNF has lysine-threonine-glutamicacid-leucine (KTEL) sequences, which closely resemble the classical ER retention signal (KDEL) [8,9]. This suggests that CDNF may have important functions in the endoplasmic reticulum (ER). The expression of CDNF in cultured primary neurons treated with ER stress-inducing agents and the protective effects of recombinant human CDNF on an oxygen–glucose depletion (OGD) cell model was investigated
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