RESUMEN
Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.
Asunto(s)
Proteínas Portadoras/metabolismo , Dendritas/metabolismo , Trastornos del Espectro Alcohólico Fetal/metabolismo , Corteza Prefrontal/metabolismo , Células Piramidales/metabolismo , Transmisión Sináptica/fisiología , Animales , Proteínas Portadoras/genética , Dendritas/efectos de los fármacos , Dendritas/patología , Modelos Animales de Enfermedad , Trastornos del Espectro Alcohólico Fetal/patología , Humanos , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación , Óxido Nítrico Sintasa de Tipo I/deficiencia , Óxido Nítrico Sintasa de Tipo I/genética , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/crecimiento & desarrollo , Corteza Prefrontal/patología , Células Piramidales/efectos de los fármacos , Células Piramidales/patologíaRESUMEN
Dermatologic care plays an important role in the transitioning process for transgender women, with changes occurring to the skin from hormone therapy (HT) and gender affirming procedures. We sought to identify knowledge gaps in a group of transgender women pertaining to both skin and hair changes during the transitioning process. The study was conducted as a cross-sectional survey. Our results demonstrate potential gaps in knowledge that transgender women have regarding HT and gender affirming procedures.