Acosta Crystal, Cortes Claudia, Altaweel Khaled, MacPhee Heather, Hoogervorst Britta, Bhullar Harpreet, MacNeil Brain, Torabi Mahmoud, Burczynski Frank, Namaka Michael Peter
College of Pharmacy, Faculty of Health Science, University of Manitoba, 750 McDermot Avenue, Winnipeg, Manitoba, Canada.
CNS Neurol Disord Drug Targets. 2015;14(8):1069-78. doi: 10.2174/1871527314666150317225205.
Nerve growth factor (NGF) expression is augmented during neuroinflammation. However, its function in the dorsal root ganglia (DRG) and spinal cord (SC) during experimental autoimmune encephalomyelitis (EAE), the inflammatory model of Multiple Sclerosis, is indistinct. Thus, the role of antigenically induced NGF in Lewis rats under a state of EAE was considered. NGF mRNA and protein expression were highly increased in DRG and SC tissues in animals with EAE. Between 18 and 24 days post induction (dpi), NGF mRNA and protein were elevated in the DRG, correlating with neurological recovery. In the SC, an increase in NGF protein at 12 dpi was, in contrast, preceded by neurological recovery. NGF mRNA expression became elevated in the SC at 15 dpi at the onset of neurological improvement and amelioration of EAE. This study revealed that antigenic induction of the 25 kDa pro-NGF isoform is associated with the disease course of EAE. Our findings suggest the induction of NGF represents an adaptive response against immune-mediated neuroinflammation in the DRG and SC that likely contributes to the EAE attenuation.
在神经炎症期间,神经生长因子(NGF)的表达会增加。然而,在实验性自身免疫性脑脊髓炎(EAE)(多发性硬化症的炎症模型)期间,其在背根神经节(DRG)和脊髓(SC)中的功能尚不清楚。因此,研究了抗原诱导的NGF在处于EAE状态的Lewis大鼠中的作用。EAE动物的DRG和SC组织中NGF mRNA和蛋白表达显著增加。诱导后18至24天(dpi),DRG中NGF mRNA和蛋白升高,与神经功能恢复相关。相比之下,在SC中,NGF蛋白在12 dpi时增加,而神经功能恢复在此之前。在神经功能改善和EAE病情缓解开始时,即15 dpi时,SC中NGF mRNA表达升高。本研究表明,25 kDa前体NGF亚型的抗原诱导与EAE的病程相关。我们的研究结果表明,NGF的诱导代表了对DRG和SC中免疫介导的神经炎症的适应性反应,这可能有助于减轻EAE。