RESUMEN
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system, but it is currently unknown whether sex is a factor in these alterations. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s) and designing early intervention strategies, we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in circadian behavioral rhythms are detectable in an animal model of the disease. Similar to BACHD males, BACHD females display circadian disruptions at both 3 and 6 months of age; however, deficits to BACHD female mouse activity levels, rhythm precision, and behavioral fragmentation are either delayed or less severe relative to males. These sex differences are associated with a smaller suprachiasmatic nucleus (SCN) in BACHD male mice at age of symptom onset (3 months), but are not associated with sex-specific differences in SCN daytime electrical activity deficits, or peptide expression (arginine vasopressin, vasoactive intestinal peptide) within the SCN. Notably, BACHD females exhibited delayed motor coordination deficits, as measured using rotarod and challenge beam. These findings suggest a sex specific factor plays a role both in non-motor and motor symptom progression for the BACHD mouse.
Asunto(s)
Ritmo Circadiano/genética , Modelos Animales de Enfermedad , Enfermedad de Huntington/fisiopatología , Ratones Transgénicos/genética , Núcleo Supraquiasmático/fisiopatología , Animales , Arginina Vasopresina/genética , Arginina Vasopresina/metabolismo , Cromosomas Artificiales Bacterianos/genética , Progresión de la Enfermedad , Femenino , Efecto Fundador , Expresión Génica , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Masculino , Ratones , Actividad Motora , Prueba de Desempeño de Rotación con Aceleración Constante , Factores Sexuales , Núcleo Supraquiasmático/anomalías , Núcleo Supraquiasmático/metabolismo , Factores de Tiempo , Péptido Intestinal Vasoactivo/genética , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
The diurnal change in baseline fetal heart rate (FHR) of four anencephalic fetuses at 20, 23, 24 and 30 weeks of gestation were examined. The mean baseline FHR in 00.00-06.00 h, 06.00-12.00 h, 12.00-18.00 h and 18.00-24.00 h were compared by one-factor ANOVA and Scheffe's test in each case. The diurnal variations in baseline FHR were recognized in all subjects (P < 0.01). In 3/4 subjects, the lowest values were at 00.00-06.00 h. The diurnal variation in baseline FHR might be caused by maternal factors because it was present even in the anencephalic fetuses that had no central nervous system having the oscillators of the circadian rhythm.