oxytocin and Craniofacial-Abnormalities

The prosocial neuropeptide oxytocin is being developed as a potential treatment for various neuropsychiatric disorders including autism spectrum disorder (ASD). Early studies using intranasal oxytocin in patients with ASD yielded encouraging results and for some time, scientists and affected families placed high hopes on the use of intranasal oxytocin for behavioral therapy in ASD. However, a recent Phase III trial obtained negative results using intranasal oxytocin for the treatment of behavioral symptoms in children with ASD. Given the frequently observed autism-like behavioral phenotypes in Prader-Willi and Schaaf-Yang syndromes, it is unclear whether oxytocin treatment represents a viable option to treat behavioral symptoms in these diseases. Here we review the latest findings on intranasal OT treatment, Prader-Willi and Schaaf-Yang syndromes, and propose novel research strategies for tailored oxytocin-based therapies for affected individuals. Finally, we propose the critical period theory, which could explain why oxytocin-based treatment seems to be most efficient in infants, but not adolescents.

Topics: Administration, Intranasal; Arthrogryposis; Autism Spectrum Disorder; Craniofacial Abnormalities; Humans; Hypopituitarism; Intellectual Disability; Oxytocin; Prader-Willi Syndrome; Research Design

Genetically modified mice mimicking ODDD (oculodentodigital dysplasia), a disease characterized by reduced Cx43 (connexin 43)-mediated gap junctional intercellular communication, represent an in vivo model to assess the role of Cx43 in mammary gland development and function. We previously reported that severely compromised Cx43 function delayed mammary gland development and impaired milk ejection in mice that harboured a G60S Cx43 mutant, yet there are no reports of lactation defects in ODDD patients. To address this further, we obtained a second mouse model of ODDD expressing an I130T Cx43 mutant to assess whether a mutant with partial gap junction channel activity would be sufficient to retain mammary gland development and function. The results of the present study show that virgin Cx43I130T/+ mice exhibited a temporary delay in ductal elongation at 4 weeks. In addition, Cx43I130T/+ mice develop smaller mammary glands at parturition due to reduced cell proliferation despite similar overall gland architecture. Distinct from Cx43G60S/+ mice, Cx43I130T/+ mice adequately produce and deliver milk to pups, suggesting that milk ejection is unaffected. Thus the present study suggests that a loss-of-function mutant of Cx43 with partial gap junction channel coupling conductance results in a less severe mammary gland phenotype, which may partially explain the lack of reported lactation defects associated with ODDD patients.

Topics: Animals; Blotting, Western; Cell Line, Tumor; Cells, Cultured; Connexin 43; Craniofacial Abnormalities; Disease Models, Animal; Epithelial Cells; Eye Abnormalities; Female; Foot Deformities, Congenital; Gap Junctions; Green Fluorescent Proteins; Humans; Lactation; Male; Mammary Glands, Animal; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Oxytocin; Point Mutation; Pregnancy; Severity of Illness Index; Syndactyly; Tooth Abnormalities