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Oxytocin Receptor Expression in Hair Follicle Stem Cells: A Promising Model for Biological and Therapeutic Discovery in Neuropsychiatric Disorders

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Abstract

The intricate nature of the human brain and the limitations of existing model systems to study molecular and cellular causes of neuropsychiatric disorders represent a major challenge for basic research. The promising progress in patient-derived stem cell technology and in our knowledge on the role of the brain oxytocin (OXT) system in health and disease offer new possibilities in that direction. In this study, the rat hair follicle stem cells (HFSCs) were isolated and expanded in vitro. The expression of oxytocin receptors (OXTR) was evaluated in these cells. The cellular viability was assessed 12 h post stimulation with OXT. The activation of OXTR-coupled intracellular signaling cascades, following OXT treatment was determined. Also, the influence of OXT on neurite outgrowth and cytoskeletal rearrangement were defined. The assessment of OXTR protein expression revealed this receptor is expressed abundantly in HFSCs. As evidenced by the cell viability assay, no adverse or cytotoxic effects were detected following 12 h treatment with different concentrations of OXT. Moreover, OXTR stimulation by OXT resulted in ERK1/2, CREB, and eEF2 activation, neurite length alterations, and cytoskeletal rearrangements that reveal the functionality of this receptor in HFSCs. Here, we introduced the rat HFSCs as an easy-to-obtain stem cell model that express functional OXTR. This cell-based model can contribute to our understanding of the progression and treatment of neuropsychiatric disorders with oxytocinergic system deficiency.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ASD :

Autism spectrum disorder

GAD :

Generalized anxiety disorder

iPSCs :

Induced pluripotent stem cells

HFSCs :

Hair follicle-derived stem cells

OXTR :

Oxytocin receptor

OXT :

Oxytocin

SNP :

Single nucleotide polymorphisms

eEF2a :

Eukaryotic elongation factor 2a

References

  1. Nestler, E. J., & Hyman, S. E. (2010). Animal models of neuropsychiatric disorders. Nature Neuroscience, 13(10), 1161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lago, S. G., Tomasik, J., & Bahn, S. (2021). Functional patient-derived cellular models for neuropsychiatric drug discovery. Translational Psychiatry, 11(1), 1–11.

    Article  Google Scholar 

  3. Haggarty, S. J., Silva, M. C., Cross, A., Brandon, N. J., & Perlis, R. H. (2016). Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models. Molecular and Cellular Neuroscience, 73, 104–115.

    Article  CAS  PubMed  Google Scholar 

  4. Paşca, S. P., Panagiotakos, G., & Dolmetsch, R. E. (2014). Generating human neurons in vitro and using them to understand neuropsychiatric disease. Annual Review of Neuroscience, 37, 479–501.

    Article  PubMed  Google Scholar 

  5. Adegbola, A., Bury, L. A., Fu, C., Zhang, M., & Wynshaw-Boris, A. (2017). Concise review: Induced pluripotent stem cell models for neuropsychiatric diseases. Stem Cells Translational Medicine, 6(12), 2062–2070.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Haggarty, S. J., & Perlis, R. H. (2014). Translation: Screening for novel therapeutics with disease-relevant cell types derived from human stem cell models. Biological Psychiatry, 75(12), 952–960.

    Article  CAS  PubMed  Google Scholar 

  7. Wang, M., Zhang, L., & Gage, F. H. (2020). Modeling neuropsychiatric disorders using human induced pluripotent stem cells. Protein & Cell, 11(1), 45–59.

    Article  CAS  Google Scholar 

  8. Hoffman, G. E., Schrode, N., Flaherty, E., & Brennand, K. J. (2019). New considerations for hiPSC-based models of neuropsychiatric disorders. Molecular Psychiatry, 24(1), 49–66.

    Article  CAS  PubMed  Google Scholar 

  9. Kampmann, M. (2020). CRISPR-based functional genomics for neurological disease. Nature Reviews Neurology, 16(9), 465–480.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Soliman, M., Aboharb, F., Zeltner, N., & Studer, L. (2017). Pluripotent stem cells in neuropsychiatric disorders. Molecular Psychiatry, 22(9), 1241–1249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C., & Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463(7284), 1035–1041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang, N., Ng, Y. H., Pang, Z. P., Südhof, T. C., & Wernig, M. (2011). Induced neuronal cells: How to make and define a neuron. Cell Stem Cell, 9(6), 517–525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pandamooz, S., Naji, M., Alinezhad, F., Zarghami, A., & Pourghasem, M. (2013). The influence of cerebrospinal fluid on epidermal neural crest stem cells may pave the path for cell-based therapy. Stem Cell Research & Therapy, 4(4), 1–9.

    Article  Google Scholar 

  14. Pandamooz, S., Salehi, M. S., Zibaii, M. I., Ahmadiani, A., Nabiuni, M., & Dargahi, L. (2018). Epidermal neural crest stem cell-derived glia enhance neurotrophic elements in an ex vivo model of spinal cord injury. Journal of Cellular Biochemistry, 119(4), 3486–3496.

    Article  CAS  PubMed  Google Scholar 

  15. Pandamooz, S., Jafari, A., Salehi, M. S., Jurek, B., Ahmadiani, A., Safari, A., et al. (2020). Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture. Biotechnology and Bioengineering, 117(2), 305–317.

    Article  CAS  PubMed  Google Scholar 

  16. Salehi, M. S., Pandamooz, S., Safari, A., Jurek, B., Tamadon, A., Namavar, M. R., et al. (2020). Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke. CNS Neuroscience & Therapeutics, 26(7), 670–681.

    Article  CAS  Google Scholar 

  17. Karimi-Haghighi, S., Pandamooz, S., Jurek, B., Fattahi, S., Safari, A., Azarpira, N., et al. (2023). From hair to the brain: The short-term therapeutic potential of human hair follicle-derived stem cells and their conditioned medium in a rat model of stroke. Molecular Neurobiology, 60, 2587–2601.

    Article  CAS  PubMed  Google Scholar 

  18. Mousavi, S. M., Akbarpour, B., Karimi-Haghighi, S., Pandamooz, S., Belém-Filho, I. J. A., Masís-Calvo, M., et al. (2022). Therapeutic potential of hair follicle-derived stem cell intranasal transplantation in a rat model of ischemic stroke. BMC Neuroscience, 23, 47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hu, Y. F., Zhang, Z. J., & Sieber-Blum, M. (2006). An epidermal neural crest stem cell (EPI-NCSC) molecular signature. Stem Cells, 24(12), 2692–2702.

    Article  CAS  PubMed  Google Scholar 

  20. Jurek, B., & Meyer, M. (2020). Anxiolytic and anxiogenic? how the transcription factor MEF2 might explain the manifold behavioral effects of oxytocin. Frontiers in Endocrinology, 11, 186.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Grinevich, V., & Neumann, I. D. (2021). Brain oxytocin: How puzzle stones from animal studies translate into psychiatry. Molecular Psychiatry, 26(1), 265–279.

    Article  CAS  PubMed  Google Scholar 

  22. Neumann, I. D., & Landgraf, R. (2012). Balance of brain oxytocin and vasopressin: Implications for anxiety, depression, and social behaviors. Trends in Neurosciences, 35(11), 649–659.

    Article  CAS  PubMed  Google Scholar 

  23. Romano, A., Tempesta, B., Micioni Di Bonaventura, M. V., & Gaetani, S. J. F. I. N. (2016). From autism to eating disorders and more: the role of oxytocin in neuropsychiatric disorders. Frontiers in Neuroscience, 9, 497.

    Article  PubMed  PubMed Central  Google Scholar 

  24. LoParo, D., & Waldman, I. J. M. P. (2015). The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: A meta-analysis. Molecular Psychiatry, 20(5), 640–646.

    Article  CAS  PubMed  Google Scholar 

  25. Baribeau, D. A., Dupuis, A., Paton, T. A., Scherer, S. W., Schachar, R. J., Arnold, P. D., et al. (2017). Oxytocin receptor polymorphisms are differentially associated with social abilities across neurodevelopmental disorders. Scientific Reports, 7(1), 1–11.

    Article  CAS  Google Scholar 

  26. Kimura, R., Tomiwa, K., Inoue, R., Suzuki, S., Nakata, M., Awaya, T., et al. (2020). Dysregulation of the oxytocin receptor gene in Williams syndrome. Psychoneuroendocrinology, 115, 104631.

    Article  CAS  PubMed  Google Scholar 

  27. Ziegler, C., Dannlowski, U., Bräuer, D., Stevens, S., Laeger, I., Wittmann, H., et al. (2015). Oxytocin receptor gene methylation: Converging multilevel evidence for a role in social anxiety. Neuropsychopharmacology, 40(6), 1528–1538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Uhrig, S., Hirth, N., Broccoli, L., von Wilmsdorff, M., Bauer, M., Sommer, C., et al. (2016). Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study. Schizophrenia Research, 177(1–3), 59–66.

    Article  PubMed  Google Scholar 

  29. Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., et al. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7(1), 1–13.

    Article  Google Scholar 

  30. Lee, M. R., Sheskier, M., Farokhnia, M., Feng, N., Marenco, S., Lipska, B., et al. (2018). Oxytocin receptor mRNA expression in dorsolateral prefrontal cortex in major psychiatric disorders: A human post-mortem study. Psychoneuroendocrinology, 96, 143–147.

    Article  CAS  PubMed  Google Scholar 

  31. King, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. J. B. P. (2016). Variation in the oxytocin receptor gene predicts brain region–specific expression and social attachment. Biological Psychiatry, 80(2), 160–169.

    Article  CAS  PubMed  Google Scholar 

  32. Danoff, J. S., Wroblewski, K. L., Graves, A. J., Quinn, G. C., Perkeybile, A. M., Kenkel, W. M., et al. (2021). Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression. Clinical Epigenetics, 13(1), 1–16.

    Article  Google Scholar 

  33. Takayanagi, Y., Yoshida, M., Bielsky, I. F., Ross, H. E., Kawamata, M., Onaka, T., et al. (2005). Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 102(44), 16096–16101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wei, J., Ma, L., Ju, P., Yang, B., Wang, Y.-X., & Chen, J. (2020). Involvement of oxytocin receptor/Erk/MAPK signaling in the mPFC in early life stress-induced autistic-like behaviors. Frontiers in Cell and Developmental Biology, 8, 564485.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Horiai, M., Otsuka, A., Hidema, S., Hiraoka, Y., Hayashi, R., Miyazaki, S., et al. (2020). Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models. Scientific Reports, 10(1), 1–13.

    Article  Google Scholar 

  36. Tomizawa, K., Iga, N., Lu, Y.-F., Moriwaki, A., Matsushita, M., Li, S.-T., et al. (2003). Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nature Neuroscience, 6(4), 384–390.

    Article  CAS  PubMed  Google Scholar 

  37. Jurek, B., Slattery, D. A., Maloumby, R., Hillerer, K., Koszinowski, S., Neumann, I. D., et al. (2012). Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats. PLoS ONE, 7(5), e37060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jurek, B., Slattery, D. A., Hiraoka, Y., Liu, Y., Nishimori, K., Aguilera, G., et al. (2015). Oxytocin regulates stress-induced Crf gene transcription through CREB-regulated transcription coactivator 3. Journal of Neuroscience, 35(35), 12248–12260.

    Article  CAS  PubMed  Google Scholar 

  39. Martinetz, S., Meinung, C.-P., Jurek, B., von Schack, D., van den Burg, E. H., Slattery, D. A., et al. (2019). De novo protein synthesis mediated by the eukaryotic elongation factor 2 is required for the anxiolytic effect of oxytocin. Biological Psychiatry, 85(10), 802–811.

    Article  CAS  PubMed  Google Scholar 

  40. Flavell, S. W., Cowan, C. W., Kim, T.-K., Greer, P. L., Lin, Y., Paradis, S., et al. (2006). Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, 311(5763), 1008–1012.

    Article  CAS  PubMed  Google Scholar 

  41. Schildge, S., Bohrer, C., Beck, K., Schachtrup, C. (2013). Isolation and culture of mouse cortical astrocytes. Journal of visualized experiments, 71, 50079.

  42. Pandamooz, S., Jurek, B., Dianatpour, M., Haerteis, S., Limm, K., Oefner, P. J., et al. (2023). The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells. Cell Proliferation, 56(7), e13397.

  43. Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., et al. (2009). The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments. Clinical Chemistry, 55(4), 611–622.

    Article  CAS  PubMed  Google Scholar 

  44. Di Benedetto, A., Sun, L., Zambonin, C. G., Tamma, R., Nico, B., Calvano, C. D., et al. (2014). Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin receptor. Proceedings of the National Academy of Sciences, 111(46), 16502–16507.

    Article  Google Scholar 

  45. Conti, F., Sertic, S., Reversi, A., & Chini, B. (2009). Intracellular trafficking of the human oxytocin receptor: Evidence of receptor recycling via a Rab4/Rab5 “short cycle.” American Journal of Physiology-Endocrinology and Metabolism, 296(3), E532–E542.

    Article  CAS  PubMed  Google Scholar 

  46. Meyer, M., Jurek, B., Alfonso-Prieto, M., Ribeiro, R., Milenkovic, V. M., Winter, J., et al. (2022). Structure-function relationships of the disease-linked A218T oxytocin receptor variant. Molecular Psychiatry, 27(2), 907–917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jurek, B., & Neumann, I. D. (2018). The oxytocin receptor: From intracellular signaling to behavior. Physiological Reviews, 98(3), 1805–1908.

    Article  CAS  PubMed  Google Scholar 

  48. Tojkander, S., Ciuba, K., & Lappalainen, P. (2018). CaMKK2 regulates mechanosensitive assembly of contractile actin stress fibers. Cell Reports, 24(1), 11–19.

    Article  CAS  PubMed  Google Scholar 

  49. Winter, J., & Jurek, B. (2019). The interplay between oxytocin and the CRF system: Regulation of the stress response. Cell and Tissue Research, 375(1), 85–91.

    Article  CAS  PubMed  Google Scholar 

  50. Winter, J., Meyer, M., Berger, I., Royer, M., Bianchi, M., Kuffner, K., et al. (2021). Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety. Molecular Psychiatry. https://doi.org/10.1038/s41380-021-01141-x

  51. Greenwood, M. A., & Hammock, E. A. (2017). Oxytocin receptor binding sites in the periphery of the neonatal mouse. PLoS ONE, 12(2), e0172904.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Greenwood, M. A., & Hammock, E. A. (2019). Oxytocin receptor binding sites in the periphery of the neonatal prairie vole. Frontiers in Neuroscience, 13, 474.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Wahis, J., Baudon, A., Althammer, F., Kerspern, D., Goyon, S., Hagiwara, D., et al. (2021). Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents. Nature Neuroscience, 24(4), 529–541.

    Article  CAS  PubMed  Google Scholar 

  54. Van Den Burg, E. H., Stindl, J., Grund, T., Neumann, I. D., & Strauss, O. (2015). Oxytocin stimulates extracellular Ca2+ influx through TRPV2 channels in hypothalamic neurons to exert its anxiolytic effects. Neuropsychopharmacology, 40(13), 2938–2947.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Amoh, Y., Li, L., Katsuoka, K., Penman, S., & Hoffman, R. M. (2005). Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proceedings of the National Academy of Sciences of the United States of America, 102(15), 5530–5534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Narytnyk, A., Verdon, B., Loughney, A., Sweeney, M., Clewes, O., Taggart, M. J., et al. (2014). Differentiation of human epidermal neural crest stem cells (hEPI-NCSC) into virtually homogenous populations of dopaminergic neurons. Stem Cell Reviews and Reports, 10(2), 316–326.

    Article  CAS  PubMed  Google Scholar 

  57. Yamane, M., Takaoka, N., Obara, K., Shirai, K., Aki, R., Hamada, Y., et al. (2021). Hair-follicle-associated pluripotent (HAP) stem cells can extensively differentiate to tyrosine-hydroxylase-expressing dopamine-secreting neurons. Cells, 10(4), 864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Lin, H., Liu, F., Zhang, C., Zhang, Z., Guo, J., Ren, C., et al. (2009). Pluripotent hair follicle neural crest stem-cell-derived neurons and schwann cells functionally repair sciatic nerves in rats. Molecular Neurobiology, 40(3), 216–223.

    Article  CAS  PubMed  Google Scholar 

  59. Sakaue, M., & Sieber-Blum, M. (2015). Human epidermal neural crest stem cells as a source of Schwann cells. Development, 142(18), 3188–3197.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Pournajaf, S., Valian, N., Shalmani, L. M., Khodabakhsh, P., Jorjani, M., & Dargahi, L. (2020). Fingolimod increases oligodendrocytes markers expression in epidermal neural crest stem cells. European Journal of Pharmacology, 885, 173502.

    Article  CAS  PubMed  Google Scholar 

  61. Khodabakhsh, P., Pournajaf, S., Mohaghegh Shalmani, L., Ahmadiani, A., & Dargahi, L. (2021). Insulin promotes Schwann-like cell differentiation of rat epidermal neural crest stem cells. Molecular Neurobiology, 58(10), 5327–5337.

    Article  CAS  PubMed  Google Scholar 

  62. Hu, Y. F., Gourab, K., Wells, C., Clewes, O., Schmit, B. D., & Sieber-Blum, M. (2010). Epidermal neural crest stem cell (EPI-NCSC)—mediated recovery of sensory function in a mouse model of spinal cord injury. Stem Cell Reviews and Reports, 6(2), 186–198.

    Article  PubMed  Google Scholar 

  63. Obara, K., Shirai, K., Hamada, Y., Arakawa, N., Yamane, M., Takaoka, N., et al. (2022). Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine. PLoS ONE, 17(1), e0262755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li, Y., Yao, D., Zhang, J., Liu, B., Zhang, L., Feng, H., et al. (2017). The effects of epidermal neural crest stem cells on local inflammation microenvironment in the defected sciatic nerve of rats. Frontiers in Molecular Neuroscience, 10, 133.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zhang, L., Li, B., Liu, B., & Dong, Z. (2019). Co-transplantation of epidermal neural crest stem cells and olfactory ensheathing cells repairs sciatic nerve defects in rats. Frontiers in Cellular Neuroscience, 13, 253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mousavi, S. M., Akbarpour, B., Karimi-Haghighi, S., Pandamooz, S., Belém-Filho, I. J. A., Masís-Calvo, M., et al. (2022). Therapeutic potential of hair follicle-derived stem cell intranasal transplantation in a rat model of ischemic stroke. BMC Neuroscience, 23(1), 1–14.

    Article  Google Scholar 

  67. Zhang, X., Tang, H., Mao, S., Li, B., Zhou, Y., Yue, H., et al. (2020). Transplanted hair follicle stem cells migrate to the penumbra and express neural markers in a rat model of cerebral ischaemia/reperfusion. Stem Cell Research & Therapy, 11(1), 1–12.

    Article  Google Scholar 

  68. Akbari, S., Hooshmandi, E., Bayat, M., Haghighi, A. B., Salehi, M. S., Pandamooz, S., et al. (2022). The neuroprotective properties and therapeutic potential of epidermal neural crest stem cells transplantation in a rat model of vascular dementia. Brain Research, 1776, 147750.

    Article  CAS  PubMed  Google Scholar 

  69. Quadrato, G., Brown, J., & Arlotta, P. (2016). The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nature Medicine, 22(11), 1220–1228.

    Article  CAS  PubMed  Google Scholar 

  70. Salehi, M. S., Neumann, I. D., Jurek, B., & Pandamooz, S. (2021) Co-stimulation of oxytocin and arginine-vasopressin receptors affect hypothalamic neurospheroid size. International Journal of Molecular Sciences, 22(16), 8464.

  71. Lestanova, Z., Bacova, Z., Kiss, A., Havranek, T., Strbak, V., & Bakos, J. (2016). Oxytocin increases neurite length and expression of cytoskeletal proteins associated with neuronal growth. Journal of Molecular Neuroscience, 59(2), 184–192.

    Article  CAS  PubMed  Google Scholar 

  72. Lestanova, Z., Puerta, F., Alanazi, M., Bacova, Z., Kiss, A., Castejon, A., et al. (2017). Downregulation of oxytocin receptor decreases the length of projections stimulated by retinoic acid in the U-87MG cells. Neurochemical Research, 42(4), 1006–1014.

    Article  CAS  PubMed  Google Scholar 

  73. Zatkova, M., Reichova, A., Bacova, Z., Strbak, V., Kiss, A., & Bakos, J. (2018). Neurite outgrowth stimulated by oxytocin is modulated by inhibition of the calcium voltage-gated channels. Cellular and Molecular Neurobiology, 38(1), 371–378.

    Article  CAS  PubMed  Google Scholar 

  74. Zatkova, M., Bacova, Z., Puerta, F., Lestanova, Z., Alanazi, M., Kiss, A., et al. (2018). Projection length stimulated by oxytocin is modulated by the inhibition of calcium signaling in U-87MG cells. Journal of Neural Transmission, 125(12), 1847–1856.

    Article  CAS  PubMed  Google Scholar 

  75. Meyer, M., Berger, I., Winter, J., & Jurek, B. (2018). Oxytocin alters the morphology of hypothalamic neurons via the transcription factor myocyte enhancer factor 2A (MEF-2A). Molecular and Cellular Endocrinology, 477, 156–162.

    Article  CAS  PubMed  Google Scholar 

  76. Meyer, M., Kuffner, K., Winter, J., Neumann, I. D., Wetzel, C. H., & Jurek, B. (2020). Myocyte enhancer factor 2A (MEF2A) defines oxytocin-induced morphological effects and regulates mitochondrial function in neurons. International Journal of Molecular Sciences, 21(6), 2200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bakos, J., Strbak, V., Paulikova, H., Krajnakova, L., Lestanova, Z., & Bacova, Z. (2013). Oxytocin receptor ligands induce changes in cytoskeleton in neuroblastoma cells. Journal of Molecular Neuroscience, 50(3), 462–468.

    Article  CAS  PubMed  Google Scholar 

  78. Gimpl, G., & Fahrenholz, F. (2001). The oxytocin receptor system: Structure, function, and regulation. Physiological Reviews, 81(2), 629–683.

    Article  CAS  PubMed  Google Scholar 

  79. Wang, Y.-F., & Hatton, G. I. (2007). Interaction of extracellular signal-regulated protein kinase 1/2 with actin cytoskeleton in supraoptic oxytocin neurons and astrocytes: Role in burst firing. Journal of Neuroscience, 27(50), 13822–13834.

    Article  CAS  PubMed  Google Scholar 

  80. Parker, K. J., Oztan, O., Libove, R. A., Sumiyoshi, R. D., Jackson, L. P., Karhson, D. S., et al. (2017). Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proceedings of the National Academy of Sciences of the United States of America, 114(30), 8119–8124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Griesi-Oliveira, K., Suzuki, A. M., Alves, A. Y., Mafra, A. C. C. N., Yamamoto, G. L., Ezquina, S., et al. (2018). Actin cytoskeleton dynamics in stem cells from autistic individuals. Scientific Reports, 8(1), 1–10.

    Article  CAS  Google Scholar 

  82. Unterholzner, J., Millischer, V., Wotawa, C., Sawa, A., & Lanzenberger, R. (2021). Making sense of patient-derived iPSCs, transdifferentiated neurons, olfactory neuronal cells, and cerebral organoids as models for psychiatric disorders. International Journal of Neuropsychopharmacology, 24(10), 759–775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Masuda, K., Han, X., Kato, H., Sato, H., Zhang, Y., Sun, X., et al. (2021). Dental pulp-derived mesenchymal stem cells for modeling genetic disorders. International Journal of Molecular Sciences, 22(5), 2269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Borgmann-Winter, K., Willard, S., Sinclair, D., Mirza, N., Turetsky, B., Berretta, S., et al. (2015). Translational potential of olfactory mucosa for the study of neuropsychiatric illness. Translational Psychiatry, 5(3), e527–e527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was financially supported by Deutsche Forschungsgemeinschaft (IDN: Ne465/27–1, Ne465/31–1 BJ: JU3039-1), the DFG-GRK 2174 and Iran National Science Foundation (INSF, grant No: 99013300) and Shiraz University of Medical Sciences (Grant No: 27044). Partial support was also provided by International Brain Research Organization (IBRO) Research Fellowship award received by the Mohammad Saied Salehi. The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Authors and Affiliations

  1. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sareh Pandamooz & Mehdi Dianatpour

  2. Department of Molecular and Behavioural Neurobiology, University of Regensburg, Regensburg, Germany

    Sareh Pandamooz, Mohammad Saied Salehi, Benjamin Jurek, Carl-Philipp Meinung & Inga D. Neumann

  3. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Saied Salehi

  4. Research Group Neurobiology of Stress Resilience, Max Planck Institute of Psychiatry, Munich, Germany

    Benjamin Jurek

  5. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Negar Azarpira

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  1. Sareh Pandamooz
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Contributions

SP, MSS and CPM conceptualized the study, performed experiments, analysed the data, and prepared the manuscript draft. BJ, NA and MD involved in manuscript writing, study design, and reviewed and edited the manuscript. IDN substantially reviewed and edited the manuscript and supervised the study and the manuscript.

Corresponding authors

Correspondence to Mohammad Saied Salehi or Inga D. Neumann.

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Ethics Approval and Consent to Participate

This project entitled “Evaluation of oxytocin effect on hair follicle-derived stem cells” was approved by the Animal Care Committee of Shiraz University of Medical Sciences, Shiraz, Iran (Approval number: IR.SUMS.AEC.1401.111). All eight rats used in this study were euthanized under CO2 inhalation in accordance with Guide for the Care and Use of Laboratory Animals by the National Institutes of Health, Bethesda, MD, USA, and approved by the government of the Oberpfalz, Germany. Hair follicles and cortical tissues were immediately obtained from euthanized animals. No experiment was performed on animals. The study is reported in accordance with ARRIVE guidelines.

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The authors declare that they have no competing interests.

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Pandamooz, S., Salehi, M.S., Jurek, B. et al. Oxytocin Receptor Expression in Hair Follicle Stem Cells: A Promising Model for Biological and Therapeutic Discovery in Neuropsychiatric Disorders. Stem Cell Rev and Rep 19, 2510–2524 (2023). https://doi.org/10.1007/s12015-023-10603-4

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