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The neurohormone oxytocin (OXT) has been implicated in the regulation of social behavior and is intensively investigated as a potential therapeutic treatment in neurodevelopmental disorders characterized by social deficits. In the Magel2-knockout (KO) mouse, a model of Schaaf-Yang Syndrome, an early postnatal administration of OXT rescued autistic-like behavior and cognition at adulthood, making this model relevant for understanding the actions of OXT in (re)programming postnatal brain development. The oxytocin receptor (OXTR), the main brain target of OXT, was dysregulated in the hippocampus of Magel2-KO adult males, and normalized upon OXT treatment at birth. Here we have analyzed male and female Magel2-KO brains at postnatal day 8 (P8) and at postnatal day 90 (P90), investigating age, genotype and OXT treatment effects on OXTR levels in several regions of the brain. We found that, at P8, male and female Magel2-KOs displayed a widespread, substantial, down-regulation of OXTR levels compared to wild type (WT) animals. Most intriguingly, the postnatal OXT treatment did not affect Magel2-KO OXTR levels at P8 and, consistently, did not rescue the ultrasonic vocalization deficits observed at this age. On the contrary, the postnatal OXT treatment reduced OXTR levels at P90 in male Magel2-KO in a region-specific way, restoring normal OXTR levels in regions where the Magel2-KO OXTR was upregulated (central amygdala, hippocampus and piriform cortex). Interestingly, Magel2-KO females, previously shown to lack the social deficits observed in Magel2-KO males, were characterized by a different trend in receptor expression compared to males; as a result, the dimorphic expression of OXTR observed in WT animals, with higher OXTR expression observed in females, was abolished in Magel2-KO mice. In conclusion, our data indicate that in Magel2-KO mice, OXTRs undergo region-specific modifications related to age, sex and postnatal OXT treatment. These results are instrumental to design precisely-timed OXT-based therapeutic strategies that, by acting at specific brain regions, could modify the outcome of social deficits in Schaaf-Yang Syndrome patients.

Muscle parameters are recommended as diagnostic criteria for malnutrition and sarcopenia in various guidelines. However, little is known about the application of muscle parameters in daily practice of nutritional care. The aim of this study was to investigate the current practice of the application of muscle parameters, along with its promoting factors and barriers by dietitians in Switzerland. A 29-item literature-based online survey was developed and distributed via the Swiss professional association of dietitians. The data were analyzed descriptively, and relationships between demographic data and usage were examined. Dietitians (n = 117) from all three language regions completed the survey and were included in the analysis. Musculature was classified as important for the assessment of nutritional status. Body weight (89.7%), handgrip strength (87.2%), bioimpedance analysis (BIA) (87.1%) and Body Mass Index (66.7%) were considered as most significant for evaluation of nutritional status. Seventy-point nine percent (70.9%) of dietitians include at least one muscle parameter in their assessment; BIA was the parameter most often included (73.5%). However, the frequency of use of muscle parameter in daily practice was rather low. Only 23.1% applied BIA on a weekly basis. Lack of knowledge (78.6%), practical experience (71.8%) and lack of equipment (77.8%) were most frequently stated as barriers for usage. The general application of muscle parameters in nutritional care is still lacking. There is an opportunity to further strengthen diagnosis and patient monitoring via a stronger application of muscle parameters in daily practice. Practical training and education could help promote their application.

1Nÿ 8D14% .=70 ÿ ,% #47% >()) (ÿ 8D14% .=7R ÿ _GD-.'(1ÿ ÿ ÿ ab ÿ def b g h g eiÿ jkÿ leef ÿ f emg eno ÿ g pÿ b qeÿ rsb qaf t h s`ief u ÿ vw w ÿ f g xqb pÿ f epef meiu ÿ yaÿ f espeÿ rw w aneiÿ ng b qasb ÿ lef zg ppg a`u ÿ {qeÿ dalkf g xqb ÿ qaw ief ÿ h af ÿ b qg pÿ lf elf gb ÿ | nqg dqÿ nrp b qg pÿ mef pg a`ÿ lapb eiÿ }edezjef ÿ ÿ ~u ÿ ÿ qb b lp t t iag u af xtũ~~t iag ÿ jg ag mÿ lf elf gb ÿ; Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage is unknown. Here we investigated cool thermosensibility during the first week of mouse life. In response to cool temperature exposure control neonates undertake innate behaviors by eliciting low-latency ultrasonic vocalization. However, we found that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool stimuli while long-term thermoregulatory function, namely nonshivering thermogenesis, is active. Investigation of the sensory pathway revealed abnormal cool-induced response in the medial preoptic area. Importantly, intranasal administration of oxytocin can rescue this thermosensory reactivity. In addition, chemogenetic inactivation in control neonates of hypothalamic oxytocin neurons reproduces the coolness response failure observed in Magel2 mutants. Collectively, these findings establish for the first-time impairments of thermal lower-reactivity in a mouse model of ASD with deletion of Magel2 gene during early life period and reveal that the oxytocinergic system regulates this neonatal cool thermosensibility.

International audience; The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.

Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain.