Oxidative stress in immune-mediated motoneuron destruction.
Experimental autoimmune gray matter disease (EAGMD) is a model of both upper and lower motor neuron degeneration. EAGMD and amyotrophic lateral sclerosis (ALS) possess similar clinical and pathological features. The aim of this study was to find evidence of upper and lower neuronal damage in the EAGMD guinea pigs. The main ultrastructural alterations included abnormal mitochondria and disorganization of neurofilaments in the myelinated nerve fibers of the spinal cord. Swollen mitochondria and dilated endoplasmic reticulum were found in pyramidal cells of the motor cortex. The myelinated fibers in the cerebral peduncle showed atrophied axons and swollen mitochondria. Some motoneurons showed apoptosis-like signs. Pathological changes in the sciatic nerve manifest wallerian-like degeneration. Using immunofluorescence double labeling and confocal laser microscopy, IgG was colocalized with activated microglia in the ventral horn of the spinal cord. We also examined possible evidences of oxidative stress in the EAGMD guinea pig model and the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in motor neuron degeneration. Our findings suggest that nitric oxide and peroxynitrite-mediated oxidative damage may play important roles in the pathogenesis of the neuronal degeneration in the spinal cord. Inflammatory cytokines such as TNF-alpha and IL-1 play important roles in the formation and acceleration of the spinal cord damage. The activation of p38MAPK signal pathway was involved in the development of the motor neuron degeneration of the spinal cord.
Xu
Lei
L
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Guo
Yan-Su
YS
Liu
Ya-Ling
YL
Wu
Shu-Yu
SY
Yang
Cheng
C
Wu
Dong-Xia
DX
Wu
Hong-Ran
HR
Zhang
Yue-Shen
YS
Li
Chun-Yan
CY
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002417:Cattle; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D016472:Motor Neuron Disease / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017966:Pyramidal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020426:Sciatic Neuropathy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases