The Pivotal Role of Oxytocin's Mechanism of Thermoregulation in Prader-Willi Syndrome, Schaaf-Yang Syndrome, and Autism Spectrum Disorder.

Oxytocin (Oxt) regulates thermogenesis, and altered thermoregulation results in Prader-Willi syndrome (PWS), Schaaf-Yang syndrome (SYS), and Autism spectrum disorder (ASD). PWS is a genetic disorder caused by the deletion of the paternal allele of 15q11-q13, the maternal uniparental disomy of chromosome 15, or defects in the imprinting center of chromosome 15. PWS is characterized by hyperphagia, obesity, low skeletal muscle tone, and autism spectrum disorder (ASD). Oxt also increases muscle tonicity and decreases proteolysis while PWS infants are hypotonic and require assisted feeding in early infancy. This evidence inspired us to merge the results of almost 20 years of studies and formulate a new hypothesis according to which the disruption of Oxt's mechanism of thermoregulation manifests in PWS, SYS, and ASD through thermosensory abnormalities and skeletal muscle tone. This review will integrate the current literature with new updates on PWS, SYS, and ASD and the recent discoveries on Oxt's regulation of thermogenesis to advance the knowledge on these diseases.

The Long Way of Oxytocin from the Uterus to the Heart in 70 Years from Its Discovery.

The research program on oxytocin started in 1895, when Oliver and Schafer reported that a substance extracted from the pituitary gland elevates blood pressure when injected intravenously into dogs. Dale later reported that a neurohypophysial substance triggers uterine contraction, lactation, and antidiuresis. Purification of this pituitary gland extracts revealed that the vasopressor and antidiuretic activity could be attributed to vasopressin, while uterotonic and lactation activity could be attributed to oxytocin. In 1950, the amino-acid sequences of vasopressin and oxytocin were determined and chemically synthesized. Vasopressin (CYFQNCPRG-NH2) and oxytocin (CYIQNCPLG-NH2) differ by two amino acids and have a disulfide bridge between the cysteine residues at position one and six conserved in all vasopressin/oxytocin-type peptides. This characterization of oxytocin led to the Nobel Prize awarded in 1955 to Vincent du Vigneaud. Nevertheless, it was only 50 years later when the evidence that mice depleted of oxytocin or its receptor develop late-onset obesity and metabolic syndrome established that oxytocin regulates energy and metabolism. Oxytocin is anorexigenic and regulates the lean/fat mass composition in skeletal muscle. Oxytocin's effect on muscle is mediated by thermogenesis via a pathway initiated in the myocardium. Oxytocin involvement in thermogenesis and muscle contraction is linked to Prader-Willi syndrome in humans, opening exciting therapeutic avenues.

Osteoblasts cultured on three-dimensional synthetic hydroxyapatite implanted on a chick allantochorial membrane induce ectopic bone marrow differentiation.

Osteoblast (OB) activities have been studied on hydroxyapatite three-dimensional (3D) scaffolds in comparison with traditional planar substrata. OBs cultured on 3D displayed increased proliferation, differentiation, and matrix protein synthesis, when compared to 2D cultures on the same substrata. Confluent cultures, however, could not be maintained for long, due to insufficient fluid diffusion within 3D scaffolds that impaired cell viability. Thus, confluent OB 3D cultures were implanted on the allantochorial membrane of chick embryos. Vessels from the embryo colonized the bone-like network giving rise in the presence of OBs to an ectopic bone marrow formation in the intratrabecular spaces. In the absence of OBs, when the biomaterial alone was implanted, blood vessels were still present but hematopoietic marrow was absent. In both cases osteoclasts (OCs) derived from the host were found on the implant surface. These results indicated that scaffolds with cells can be easily vascularized and confirmed the role of OBs in the definition of the microenvironment that induce blood marrow differentiation in the intratrabecular spaces.