title: Pertussis toxin attenuates experimental autoimmune encephalomyelitis by upregulating neuronal vascular endothelial growth factor.
abstract: We have reported earlier that pertussis toxin (PTx) attenuates the motor deficits in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. PTx protects neurons from inflammatory insults. Vascular endothelial growth factor (VEGF) is also neuroprotective. However, the effect of PTx on VEGF has never been studied. We investigated whether PTx modulates neuronal VEGF expression and how it affects the pathogenesis of EAE. EAE was induced by injecting myelin oligodendrocyte glycoprotein 35-55 peptides with adjuvants into C57BL/6 mice. Clinical scores of EAE were evaluated daily for 19 days. Brain and spinal cord samples were collected and assessed for inflammation and demyelination. VEGF, NeuN for neurons, and Caspase-3 for apoptosis were stained for localization using immunohistochemistry techniques, followed by western blot analysis for quantification. Primary neurons were cultured to assess the direct effect of PTx on neuronal VEGF expression. PTx treatment increases neuronal VEGF expression by up to ∼75% in vitro and ∼60% in vivo, preventing neurons from apoptosis. This leads to resolution in inflammation and remyelination and amendment in motor deficits. Our findings suggest that upregulation of endogenous neuronal VEGF by PTx protects motor deficits in EAE and it is a potential therapeutic option for multiple sclerosis.
authors: Departments of Neurology, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
authors: Zhiwei
authors: Z
authors: Tang
authors: Jun-Xiang
authors: JX
authors: Yin
authors: Pengcheng
authors: P
authors: Han
authors: Yan
authors: Y
authors: Gan
authors: Stephen W
authors: SW
authors: Coons
authors: Chongqian
authors: C
authors: Wang
authors: Marwan
authors: M
authors: Maalouf
authors: Jiong
authors: J
authors: Shi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D037342:Pertussis Toxin / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C445081:myelin oligodendrocyte glycoprotein (35-55); D037342:Pertussis Toxin