Abstract
Oxytocin (OT), the main neuropeptide of sociality, is expressed in neurons exclusively localized in the hypothalamus. During the last decade, a plethora of neuroendocrine, metabolic, autonomic and behavioral effects of OT has been reported. In the urgency to find treatments to syndromes as invalidating as autism, many clinical trials have been launched in which OT is administered to patients, including adolescents and children. However, the impact of OT on the developing brain and in particular on the embryonic and early postnatal maturation of OT neurons, has been only poorly investigated. In the present review we summarize available (although limited) literature on general features of ontogenetic transformation of the OT system, including determination, migration and differentiation of OT neurons. Next, we discuss trajectories of OT receptors (OTR) in the perinatal period. Furthermore, we provide evidence that early alterations, from birth, in the central OT system lead to severe neurodevelopmental diseases such as feeding deficit in infancy and severe defects in social behavior in adulthood, as described in Prader-Willi syndrome (PWS). Our review intends to propose a hypothesis about developmental dynamics of central OT pathways, which are essential for survival right after birth and for the acquisition of social skills later on. A better understanding of the embryonic and early postnatal maturation of the OT system may lead to better OT-based treatments in PWS or autism.
Highlights
We provide evidence that early alterations, from birth, in the central OT system lead to severe neurodevelopmental diseases such as feeding deficit in infancy and severe defects in social behavior in adulthood, as described in Prader-Willi syndrome (PWS)
Oxytocin (OT) is a neuropeptide which is synthesized in defined nuclei of the hypothalamus, paraventricular (PVN), supraoptic (SON), and accessory (AN) nuclei and secreted both in the blood circulation as a hormone and in the brain as a neuromodulator
Hundreds of original reports and reviews have been published, clearly showing that the OT system is a key regulator of all the aspects of social behavior, including those involved in reproduction and care of the offspring (Lee et al, 2009)
Summary
Oxytocin (OT) is a neuropeptide which is synthesized in defined nuclei of the hypothalamus, paraventricular (PVN), supraoptic (SON), and accessory (AN) nuclei and secreted both in the blood circulation as a hormone and in the brain as a neuromodulator. OT has been found to induce adverse behavior in Frontiers in Neuroanatomy www.frontiersin.org ontogenesis of oxytocin signaling borderline-personality disorders (Bartz et al, 2011) These results suggest that the selection of patients will play a crucial role in determining the outcome of the symptomatic treatment with this neuropeptide, the use of which should be restricted to those individuals who could benefit from it. At E14.5 dpc, the PVN and the SON are settled (Nakai et al, 1995), while AN are recognized later (probably due to their small size and relatively small number of cells; Altman and Bayer, 1978a,b,c) At this stage, an antibody recognizing the Neurophysin-I (the carrier protein for OT) reveals a positive immunosignal (Figure 1B), consistent with the expression of the OT-prohormone, not yet detected at E12.5 dpc. GENETIC HIERARCHY OF OT NEURON FORMATION The signaling molecules and transcription factors that are involved in the determination and differentiation of OT neurons are not well known, only a few mouse studies reported factors
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