RESUMEN
Corticospinal motor neurons (CSMN) are the cortical component of motor neuron circuitry, which controls voluntary movement and degenerates in diseases such as amyotrophic lateral sclerosis, primary lateral sclerosis and hereditary spastic paraplegia. By using dual labeling combined with molecular marker analysis, we identified AAV2-2 mediated retrograde transduction as an effective approach to selectively target CSMN without affecting other neuron populations both in wild-type and hSOD1(G93A) transgenic ALS mice. This approach reveals very precise details of cytoarchitectural defects within vulnerable neurons in vivo. We report that CSMN vulnerability is marked by selective degeneration of apical dendrites especially in layer II/III of the hSOD1(G93A) mouse motor cortex, where cortical input to CSMN function is vastly modulated. While our findings confirm the presence of astrogliosis and microglia activation, they do not lend support to their direct role for the initiation of CSMN vulnerability. This study enables development of targeted gene replacement strategies to CSMN in the cerebral cortex, and reveals CSMN cortical modulation defects as a potential cause of neuronal vulnerability in ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/virología , Dendritas/patología , Dependovirus/fisiología , Neuronas Motoras/patología , Tractos Piramidales/patología , Transducción de Señal/fisiología , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Dendritas/química , Dendritas/virología , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuronas Motoras/metabolismo , Neuronas Motoras/virología , Tractos Piramidales/metabolismo , Tractos Piramidales/virologíaRESUMEN
The psychosocial impact of human immunodeficiency virus (HIV) disease has been recognized since the beginning of the epidemic for affected adults, but there has been less focus on the impact of HIV on young people. Among HIV-positive (HIV+) adults, high levels of distress, psychiatric symptoms, and their associations with worse health outcomes were recognized early in the epidemic. Subsequently, many studies have focused on understanding the prevalence of psychiatric symptoms among HIV+ adults and on identifying effective treatments for these symptoms. Fewer studies have examined these symptoms and their treatments among HIV+ children and adolescents. This article reviews what is known about psychiatric syndromes among HIV+ youths, their treatments, and other psychosocial factors of concern to the psychiatrist when treating children and adolescents with HIV disease.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/psicología , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Complejo SIDA Demencia/epidemiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adolescente , Terapia Antirretroviral Altamente Activa/métodos , Niño , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Trastornos Mentales/diagnóstico , Microglía/virología , Pruebas Neuropsicológicas , Prevalencia , Tractos Piramidales/virología , Índice de Severidad de la EnfermedadAsunto(s)
Infecciones por VIH/complicaciones , VIH-1/inmunología , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/virología , Adulto , Progresión de la Enfermedad , Disartria/genética , Disartria/fisiopatología , Disartria/virología , Trastornos Neurológicos de la Marcha/genética , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/virología , VIH-1/genética , Humanos , Huésped Inmunocomprometido/genética , Huésped Inmunocomprometido/inmunología , Masculino , Persona de Mediana Edad , Corteza Motora/inmunología , Corteza Motora/fisiopatología , Corteza Motora/virología , Enfermedad de la Neurona Motora/fisiopatología , Neuronas Motoras/inmunología , Neuronas Motoras/virología , Espasticidad Muscular/genética , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/virología , Paraparesia/genética , Paraparesia/fisiopatología , Paraparesia/virología , Tractos Piramidales/inmunología , Tractos Piramidales/fisiopatología , Tractos Piramidales/virologíaAsunto(s)
Síndrome de Mioclonía Nocturna/fisiopatología , Síndrome de Mioclonía Nocturna/virología , Paraparesia Espástica Tropical/complicaciones , Paraparesia Espástica Tropical/fisiopatología , Médula Espinal/fisiopatología , Adulto , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Virus Linfotrópico T Tipo 1 Humano/fisiología , Humanos , Pierna/inervación , Pierna/fisiopatología , Imagen por Resonancia Magnética , Músculo Esquelético/inervación , Músculo Esquelético/fisiopatología , Inhibición Neural/fisiología , Síndrome de Mioclonía Nocturna/diagnóstico , Paraparesia Espástica Tropical/diagnóstico , Tractos Piramidales/patología , Tractos Piramidales/fisiopatología , Tractos Piramidales/virología , Reflejo Anormal/fisiología , Formación Reticular/fisiopatología , Médula Espinal/patología , Médula Espinal/virologíaRESUMEN
Among the enteroviruses, polioviruses and enterovirus 71 (EV71) are two major neurotropic viruses causing serious neurological manifestations. While polioviruses are being eradicated globally by vaccination, EV71 still has the potential to cause a large outbreak such as that in Taiwan in 1998, in which there were many fatalities. In this study, we determined the neurovirulence of EV71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five EV71 strains, which were isolated from individual patients with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After intraspinal inoculation, the monkeys developed neurological manifestations within 1-6 days post-inoculation, irrespective of the inoculated strains. These manifestations included not only pyramidal tract signs such as flaccid paralysis, but also extrapyramidal tract signs such as tremor and ataxia. Histological and viral examinations confirmed virus replication in the spinal cord, brainstem, cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during the 1970s and 1990s showed no particular differences with respect to neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of polioviruses.