RESUMO

Introduction: The spaceflight environment presents unique demands on human physiology; among those demands, is sleep. Sleep loss and circadian desynchronization is a major concern for future deep- exploration plans, including long-term crewed missions to the Moon and Mars. Aims: Analyze evidence of sleep disruption in crewmembers during low-Earth orbit missions, identify the use of sleep-promoting medication among crewmembers and deepen the comprehension of challenges to sleep physiology for future missions to the Moon and Mars. Results: Evidence consistently indicates a loss of sleep and circadian rhythm disruption during low-Earth orbit missions. Sleep duration is shortened especially the night before a critical operation and during circadian-misaligned sleep episodes. The prevalence of sleep-promoting medication ranges between 71% and 78%; medication is more frequently taken on circadian-misaligned sleep episodes. Regarding the Moon, Apollo astronauts had variable sleep duration. For some, sleep was restful while others had poor-quality sleep. Many reported fatigue and errors due to the lack of rest. A loss of the 24-h light/dark might be expected due to the Moon's complex illumination characteristics. Regarding Mars, one main challenge will consist in synchronizing the circadian clock to a Martian day (24.65 h).

RESUMO

El Síndrome de Rett es un trastorno monogénico ligado al cromosoma X, de carácter progresivo que afecta el neurodesarrollo principalmente de niñas durante las primeras etapas del ciclo vital. Su etiología se debe principalmente a las mutaciones de cambio de nucleótido único con pérdida de función del gen MECP2. Este gen codifica para la proteína del mismo nombre cuya principal función es actuar como un represor global de la transcripción mediante el reconocimiento de zonas metiladas de islas CpG y el reclutamiento de factores correpresores que modulan la expresión génica desacetilando histonas. Dentro de las principales alteraciones estructurales asociadas al síndrome se encuentran una morfología neuronal atípica con tamaño del soma neuronal y número de espinas dendríticas reducido, además de alteraciones neuroquímicas sobre todo en la señalización GABAérgica llevando a una desregulación entre señales excitatorias e inhibitorias, causando epilepsia. También se han descrito una serie de alteraciones metabólicas, oxidativas e inflamatorias. El tratamiento hasta ahora se ha enfocado más en buscar un alivio sintomático para las manifestaciones del síndrome pero se ha desarrollado recientemente terapia génica con el objetivo de tratar desde sus bases neurogenéticas la patología y evitar así el desarrollo alterado durante la niñez.

Rett Syndrome is a monogenic disorder linked to the X chromosome, of a progressive nature that affects neurodevelopment mainly in girls during the first stages of the life cycle. Its etiology is mainly due to loss-of-function single nucleotide change mutations of the MECP2 gene. This gene codes for the protein of the same name whose main function is to act as a global repressor of transcription through the recognition of methylated areas of CpG islands and the recruitment of corepressor factors that modulate gene expression by deacetylating histones. Among the main structural alterations associated with the syndrome are an atypical neuronal morphology with a size of the neuronal soma and a reduced number of dendritic spines, in addition to neurochemical alterations, especially in the GABAergic signal, leading to dysregulation between excitatory and inhibitory signals, causing epilepsy. A series of metabolic, oxidative, and inflammatory disorders have also been described. Until now, treatment has focused more on seeking symptomatic relief for the manifestations of the syndrome, but gene therapy has recently been developed with the aim of treating the pathology from its neurogenetic bases and thus avoiding altered development during childhood.