L Yang1, Y Jiang2, Z Wen2, X Xu2, X Xu2, J Zhu2, X Xie1, L Xu2, Y Xie2, X Liu2, G Xu3. 1. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China. 2. Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. 3. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China; Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address: gelinxu@gmail.com.
Abstract
PURPOSE: This study aimed to clarify whether ischemia-induced early growth response 1 (EGR1) influenced the outcomes of experimental stroke by regulating brain-derived neurotrophic factor (BDNF) expression. METHODS AND RESULTS: To mimic ischemia, mice were subjected to middle cerebral artery occlusion, and neurons challenged with oxygen-glucose deprivation. The expression of EGR1 was increased immediately and reached the peak 24h after reperfusion. To increase and to decrease EGR1 expressions, two types of recombinant lentiviruses were constructed. EGR1 over-expression induced by recombinant lentiviruses expanded infarct volumes and increased the numbers of terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade C-positive cells; while decreased EGR1 expression induced by recombinant lentiviruses diminished infarct volumes and decreased the numbers of TUNEL- and Fluoro-Jade C-positive cells. Both in vitro and in vivo, increasing EGR1 expression with recombinant lentiviruses lead to decreased BDNF expressions; while silencing EGR1 expression with recombinant lentiviruses lead to increased BDNF expressions. Results from electrophoretic mobility shift assay indicated that EGR1 influenced the BDNF expression by binding to its promoter. CONCLUSION: Ischemia-induced EGR1 expression may exaggerate brain injury by reducing BDNF expression. Inhibiting EGR1 may become a potential treatment for improving outcomes of ischemic stroke.
PURPOSE: This study aimed to clarify whether ischemia-induced early growth response 1 (EGR1) influenced the outcomes of experimental stroke by regulating brain-derived neurotrophic factor (BDNF) expression. METHODS AND RESULTS: To mimic ischemia, mice were subjected to middle cerebral artery occlusion, and neurons challenged with oxygen-glucose deprivation. The expression of EGR1 was increased immediately and reached the peak 24h after reperfusion. To increase and to decrease EGR1 expressions, two types of recombinant lentiviruses were constructed. EGR1 over-expression induced by recombinant lentiviruses expanded infarct volumes and increased the numbers of terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade C-positive cells; while decreased EGR1 expression induced by recombinant lentiviruses diminished infarct volumes and decreased the numbers of TUNEL- and Fluoro-Jade C-positive cells. Both in vitro and in vivo, increasing EGR1 expression with recombinant lentiviruses lead to decreased BDNF expressions; while silencing EGR1 expression with recombinant lentiviruses lead to increased BDNF expressions. Results from electrophoretic mobility shift assay indicated that EGR1 influenced the BDNF expression by binding to its promoter. CONCLUSION:Ischemia-induced EGR1 expression may exaggerate brain injury by reducing BDNF expression. Inhibiting EGR1 may become a potential treatment for improving outcomes of ischemic stroke.
Authors: Nele de Klerk; Sunil D Saroj; Gabriela M Wassing; Lisa Maudsdotter; Ann-Beth Jonsson Journal: Front Cell Infect Microbiol Date: 2017-01-25 Impact factor: 5.293