Abstract
Oxytocin (OXT) is a neuropeptide involved in a plethora of behavioral and physiological processes. However, there is a prominent lack of 3D cell culture models that investigate the effects of OXT on a cellular/molecular level. In this study, we established a hypothalamic neuronal spheroid model to investigate the cellular response in a more realistic 3D setting. Our data indicate that the formation of spheroids itself does not alter the basic characteristics of the cell line and that markers of cellular morphology and connectivity are stably expressed. We found that both OXT and arginine vasopressin (AVP) treatment increase spheroid size (surface area and volume), as well as individual nucleus size, which serves as an indicator for cellular proliferation. The cellular response to both OXT and AVP seems mainly to be mediated by the AVP receptor 1a (V1aR); however, the OXT receptor (OXTR) contributes significantly to the observed proliferative effect. When we blocked the OXTR pharmacologically or knocked down the OXTR by siRNA, the OXT- or AVP-induced cellular proliferation decreased. In summary, we established a 3D cell culture model of the neuronal response to OXT and AVP and found that spheroids react to the treatment via their respective receptors but also via cross-talk between the two receptor types.
Highlights
Published: 6 August 2021The neuropeptide oxytocin (OXT) is involved in the classical neuroendocrine regulation of physiological processes such as milk letdown or labor and of various social and emotional behaviors such as maternal behavior, anxiety, or social motivation [1,2,3].We previously showed on a cellular level that OXT regulates neuronal morphology, ATP production, and calcium signaling [4,5], which are processes that regulate neuronal connectivity
The OXT system is highly cross-linked with other neuropeptide systems; for instance, we previously showed that intranasal OXT treatment affects the GnRH, kisspeptin, and neurokinin B systems [7,8]
On cellular processes in a natural 3D environment, we first tested whether the hypothalamic neuronal cell line H32 is able to generate spheroids
Summary
Published: 6 August 2021The neuropeptide oxytocin (OXT) is involved in the classical neuroendocrine regulation of physiological processes such as milk letdown or labor and of various social and emotional behaviors such as maternal behavior, anxiety, or social motivation [1,2,3].We previously showed on a cellular level that OXT regulates neuronal morphology, ATP production, and calcium signaling [4,5], which are processes that regulate neuronal connectivity. Neuronal connectivity can be compromised in autism spectrum disorder (ASD), which might explain why some ASD patients benefit from intranasal OXT treatment [6]. The OXT system is highly cross-linked with other neuropeptide systems; for instance, we previously showed that intranasal OXT treatment affects the GnRH, kisspeptin, and neurokinin B systems [7,8]. The arginine vasopressin (AVP) system, which is evolutionarily related to the OXT system [13,14], shows cross-talk with the OXT system in a variety of different contexts, such as female aggression [15], substance use disorder [16,17], or ASD and schizophrenia [18]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
