VGF, Which Is Induced Transcriptionally in Stroke Brain, Enhances Neurite Extension and Confers Protection Against Ischemia In Vitro.
Ischemic stroke is a devastating neural event as currently no therapies other than physical rehabilitation are available to enhance recovery after stroke. To identify endogenous mediators to repair stroke brain, we performed the expression profiling analysis of transcripts in the mouse photothrombotic stroke brain. Based on real-time PCR analysis, we found VGF, identified as a nerve growth factor (NGF)-regulated transcript, was induced transcriptionally in stroke brain at 1-7 days after insult. The immunoreactivites of VGF were observed in the neurons around the ischemic core of stroke brain. Experiments with various inhibitors and plasmid transfections indicated that cAMP response element binding protein-mediated complex signaling pathways are possibly implicated in the NGF-mediated VGF expressions in vitro. Furthermore, the over-expression of VGF promoted neurite extensions and conferred protections from ischemic stress in vitro. These findings raise the possibility the application of VGF could be one of the promising therapeutic strategies to enhance recovery after stroke.
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Muneki
M
Sakamoto
Yuta
Y
Miyazaki
Keiko
K
Kitajo
Atsushi
A
Yamaguchi
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020767:Intracranial Thrombosis / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020521:Stroke / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D013997:Time Factors; D014162:Transfection
D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C510637:VGF protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D050882:CREB-Binding Protein; D010751:Phosphopyruvate Hydratase