RESUMEN
Prader-Willi syndrome is a neurogenetic disease resulting from the absence of paternal expression of several imprinted genes, including NECDIN. Prader-Willi children and adults have severe breathing defects with irregular rhythm, frequent sleep apneas, and blunted respiratory regulations. For the first time, we show that Prader-Willi infants have sleep apneas already present at birth. In parallel, in wild-type and Necdin-deficient mice, we studied the respiratory system with in vivo plethysmography, in vitro electrophysiology, and pharmacology. Because serotonin is known to contribute to CNS development and to affect maturation and function of the brainstem respiratory network, we also investigated the serotonergic system with HPLC, immunohistochemistry, Rabies virus tracing approaches, and primary culture experiments. We report first that Necdin-deficiency in mice induces central respiratory deficits reminiscent of Prader-Willi syndrome (irregular rhythm, frequent apneas, and blunted respiratory regulations), second that Necdin is expressed by medullary serotonergic neurons, and third that Necdin deficiency alters the serotonergic metabolism, the morphology of serotonin vesicles in medullary serotonergic neurons but not the number of these cells. We also show that Necdin deficiency in neonatal mice alters the serotonergic modulation of the respiratory rhythm generator. Thus, we propose that the lack of Necdin expression induces perinatal serotonergic alterations that affect the maturation and function of the respiratory network, inducing breathing deficits in mice and probably in Prader-Willi patients.
Asunto(s)
Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Respiración/genética , Serotonina/metabolismo , Síndromes de la Apnea del Sueño/fisiopatología , Adulto , Animales , Animales Recién Nacidos , Células Cultivadas , Preescolar , Modelos Animales de Enfermedad , Humanos , Lactante , Bulbo Raquídeo/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/citología , Neuronas/metabolismo , Médula Espinal/metabolismoRESUMEN
STUDY AIM: To describe general movement in extremely premature infants and examine correlations with risk factors for antenatal, perinatal, and postnatal morbidity. STUDY TYPE: Prospective, single-center study. Nineteen patients were followed up. METHODOLOGY: The infants' general movement was analyzed using video recordings. Qualitative and quantitative assessments were performed during the writhing movement (WM) period and fidgety movement (FM) period. The quality of the general movements (GMs) and the scores achieved were then correlated with antenatal, perinatal, and postnatal factors. RESULTS: Infants' motor activity fluctuated during the WM period, especially in extremely premature infants where poor repertoire is often observed. No correlations were found between WMs and obstetric factors. Gestational age correlated with WMs' quality (p=0.023). WMs correlated with factors of postnatal morbidity such as chronic lung disease (CLD) (p=0.034) and nosocomial infections (p=0.05). At 3 months corrected age, the spontaneous movement quality are correlated with neurological explorations such as US brain (p=0.032), MRI (p=0.039), EEG (p=0.036), and neurological follow-up assessments (p=0.015). CONCLUSION: Prudence must be used when performing the analysis of general movement in extremely preterm infants. WMs may be influenced by perinatal morbidity, and possibly by the severe brain immaturity of these infants. WMs correlate with CLD and nosocomial infections. Analysis of general movement in infants of 3 months corrected age is a valuable means to detect neurological disorders.
Asunto(s)
Mortalidad Infantil , Recien Nacido Prematuro , Movimiento/fisiología , Encéfalo/patología , Encéfalo/fisiología , Encéfalo/fisiopatología , Electroencefalografía , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Menopause transition is associated with an increased prevalence of metabolic syndrome (MS), which may partly explain the higher coronary heart disease risk. The aim of this study was to examine the impact of a 16-week walking program on the metabolic risk profile of women 50 to 65 years old whose body mass index ranged from 29 to 35 kg/m. METHODS: A total of 153 postmenopausal women were subjected to three sessions per week of 45-minutes of walking at 60% of their heart rate reserve. At baseline, 46 and 84 women were characterized by one and two or more determinants of MS, respectively, whereas 23 women did not show this condition. Body composition, resting blood pressure, fasting lipid-lipoprotein profile, and cardiorespiratory fitness (CRF) were measured before and after exercise. RESULTS: In the whole sample of 153 women, CRF estimated by V(O2max) increased in response to walking (P < 0.0001). Endurance training promoted body weight and fat mass losses and reduced waist girth and blood pressure, whereas it decreased plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentrations (P < 0.0001). Improvements in lipid-lipoprotein levels were not associated with increases in CRF but seemed to be dependent on reduced body fatness. However, the greatest ameliorations in metabolic risk profile were found in women characterized by two or more determinants of MS at baseline than in the two other groups (0.05 < P < 0.0001). CONCLUSION: A moderate-intensity physical activity is thus sufficient to reduce the metabolic risk profile of postmenopausal women characterized by the presence of one or several clinical features of MS but without overt coronary heart disease.
Asunto(s)
Terapia por Ejercicio , Síndrome Metabólico/terapia , Obesidad/terapia , Posmenopausia , Caminata , Anciano , Composición Corporal , Estudios de Casos y Controles , Femenino , Humanos , Hiperlipoproteinemias/terapia , Hipertensión/terapia , Persona de Mediana Edad , Consumo de OxígenoRESUMEN
The duration of the numerous weight-loss studies that combine physical activity and diet varies from 3 to 14 months, and these studies have often considered pre- and postmenopausal women separately. The purpose of this study was to compare the effects of a 3-week weight-reducing program that combines caloric restriction and exercise on the metabolic profile, eating behaviors, and perceived health of sedentary obese pre- and postmenopausal women, after adjustment for age. In 10 pre- and 22 postmenopausal women, before and after weight loss, body composition, fasting lipid-lipoprotein profile, glucose and insulin levels, eating behaviors, and perceived health state were assessed. Body mass index, fat mass, and waist girth decreased after weight reduction in both groups (p < 0.0001). Reductions in fasting serum cholesterol and low-density lipoprotein-cholesterol levels were greater in pre- than in postmenopausal women (p < 0.0001), whereas triacylglycerol, glucose, and high-density lipoprotein-cholesterol levels decreased similarly in both groups (p < 0.05). Neither fasting insulin nor free fatty-acid concentrations were modified after weight loss in either group. Disinhibition (p < 0.005) and hunger scores on the three-factor eating questionnaire (TFEQ) (p < 0.05) and the state-anxiety score on the state-trait anxiety inventory (STAI) questionnaire (p < 0.0005) decreased in both groups, but restriction (TFEQ) increased (p < 0.01) and trait anxiety (STAI) decreased (p < 0.001) after weight reduction only in premenopausal women. Improvements in selected lipid-lipoprotein indices, eating behaviors, and perceived health-state components were better in pre- than in postmenopausal women, suggesting that menopausal status has an influence on some metabolic and behavioral responses to weight loss.