RESUMEN
Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD.
Asunto(s)
Trastorno Autístico/sangre , Hipocampo/citología , Inmunoglobulina A/sangre , Inmunoglobulina A/farmacología , Proteína Básica de Mielina/inmunología , Transmisión Sináptica/efectos de los fármacos , Adolescente , Animales , Trastorno Autístico/inmunología , Trastorno Autístico/fisiopatología , Encéfalo/efectos de los fármacos , Encéfalo/inmunología , Encéfalo/metabolismo , Niño , Preescolar , Inhibidores de Cisteína Proteinasa/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunoglobulina A/efectos de los fármacos , Técnicas In Vitro , Leupeptinas/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Técnicas de Placa-Clamp , Proteolisis/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brain--such as the hippocampus, ventromedial hypothalamic nucleus, and brainstem--of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette-Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV.