RESUMEN
The adult peripheral nervous system is able to regenerate after injury. Regeneration is associated with the expression of new genes and proteins. Proteins abundant in developing axons increase in expression after injury, whereas proteins involved in neurotransmission are downregulated. It has been hypothesized that molecular mechanisms underlying regeneration-associated alterations in gene expression may be a recapitulation of developmental processes. These gene expression changes are likely to be regulated by changes in the gene expression of transcription factors. As homeobox genes play important roles in embryonic development of the nervous system, it makes them candidates for a regulatory role in the process of regeneration. Here we show that the relative mRNA expression levels of Isl1 decreased shortly after crush, but those of DRG11, Lmx1b, and Pax3 did not change after crush. These data indicate that the developmental expression patterns of the homeobox genes studied here are not recapitulated during regeneration of the dorsal root ganglia neurons. We conclude that developmental gene expression programs controlled by these homeobox genes are not directly involved in sciatic nerve regeneration.
Asunto(s)
Ganglios Espinales/fisiopatología , Genes Homeobox/genética , Regeneración Nerviosa/genética , Plasticidad Neuronal/genética , Neuronas Aferentes/metabolismo , Neuropatía Ciática/genética , Animales , Proteínas de Unión al ADN/genética , Lateralidad Funcional/genética , Ganglios Espinales/citología , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas de Homeodominio/genética , Proteínas con Homeodominio LIM , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Neuronas Aferentes/citología , Factor de Transcripción PAX3 , Factores de Transcripción Paired Box , Recuperación de la Función/genética , Neuropatía Ciática/metabolismo , Neuropatía Ciática/fisiopatología , Factores de Transcripción/genética , Regulación hacia Arriba/genéticaRESUMEN
Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are the best known forms of prion diseases. A basis for their pathogenesis is the transformation of normal prion protein to abnormal prion protein. This would mean that either loss of normal function or a gain of a toxic function of the prion protein would play a major role. Since the prime target for Creutzfeldt-Jakob disease in humans is the neocortex, and the intracortical distribution of the destructive process in prion diseases appears not to be haphazard, it may be that a clear cortical study of normal prion protein production in the premorbid human neocortex might contribute to insight in the pathogenesis of prion diseases. As no such study is available, we performed a detailed study in normal human cortex using immunohistochemistry for prion protein, in both frozen and vibratomised tissue, and in situ hybridisation for prion protein mRNA. We have found normal prion protein production mainly in the upper cortical neurons in neocortex and Purkinje cells in the cerebellum. This finding implicates that normal prion protein is more important as an anti-apoptotic signal in disease than abnormal prion protein is as a toxic substance.