Co-Stimulation of Oxytocin and Arginine-Vasopressin Receptors Affect Hypothalamic Neurospheroid Size |
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Authors: | Mohammad Saied Salehi Inga D. Neumann Benjamin Jurek Sareh Pandamooz |
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Affiliation: | 1.Clinical Neurology Research Center, Shiraz University of Medical Science, Shiraz 7193635899, Iran;2.Department of Molecular and Behavioural Neurobiology, Institute of Zoology, University of Regensburg, 93051 Regensburg, Germany;3.Institute for Molecular and Cellular Anatomy, University of Regensburg, 93051 Regensburg, Germany;4.Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran |
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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. |
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Keywords: | oxytocin spheroid proliferation OXTR V1aR cytoskeleton |
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