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.

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.

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.

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