Assuntos
Doença de Depósito de Glicogênio Tipo II/patologia , Fígado/patologia , Músculo Esquelético/patologia , Adulto , Diagnóstico Diferencial , Feminino , Glicogênio/metabolismo , Humanos , Fígado/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/patologia , Piomiosite/patologia , Adulto JovemRESUMO
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.
Assuntos
Doença dos Neurônios Motores/imunologia , Estresse Oxidativo/imunologia , Medula Espinal/imunologia , Animais , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/metabolismo , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Bovinos , Citocinas/metabolismo , Modelos Animais de Doenças , Cobaias , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/fisiopatologia , Degeneração Neural/imunologia , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Fibras Nervosas Mielinizadas/imunologia , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Óxido Nítrico/metabolismo , Ácido Peroxinitroso/metabolismo , Células Piramidais/imunologia , Células Piramidais/metabolismo , Células Piramidais/patologia , Neuropatia Ciática/imunologia , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Degeneração Walleriana/imunologia , Degeneração Walleriana/metabolismo , Degeneração Walleriana/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS- like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.
