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. 2021 May;81(4):366-388.
doi: 10.1002/dneu.22815. Epub 2021 Mar 2.

The impact of oxytocin on neurite outgrowth and synaptic proteins in Magel2-deficient mice

Alexandra Reichova  1 , Fabienne Schaller  2 , Stanislava Bukatova  1 , Zuzana Bacova  1 , Françoise Muscatelli  2 , Jan Bakos  1   3
Affiliations

The impact of oxytocin on neurite outgrowth and synaptic proteins in Magel2-deficient mice

Alexandra Reichova et al. Dev Neurobiol. 2021 May.

Abstract

Oxytocin contributes to the regulation of cytoskeletal and synaptic proteins and could, therefore, affect the mechanisms of neurodevelopmental disorders, including autism. Both the Prader-Willi syndrome and Schaaf-Yang syndrome exhibit autistic symptoms involving the MAGEL2 gene. Magel2-deficient mice show a deficit in social behavior that is rescued following the postnatal administration of oxytocin. Here, in Magel2-deficient mice, we showed that the neurite outgrowth of primary cultures of immature hippocampal neurons is reduced. Treatment with oxytocin reversed this abnormality. In the hippocampus of Magel2-deficient pups, we further demonstrated that several transcripts of neurite outgrowth-associated proteins, synaptic vesicle proteins, and cell-adhesion molecules are decreased. In the juvenile stage, when neurons are mature, normalization or even overexpression of most of these markers was observed, suggesting a delay in the neuronal maturation of Magel2-deficient pups. Moreover, we found reduced transcripts of the excitatory postsynaptic marker, Psd95 in the hippocampus and we observed a decrease of PSD95/VGLUT2 colocalization in the hippocampal CA1 and CA3 regions in Magel2-deficient mice, indicating a defect in glutamatergic synapses. Postnatal administration of oxytocin upregulated postsynaptic transcripts in pups; however, it did not restore the level of markers of glutamatergic synapses in Magel2-deficient mice. Overall, Magel2 deficiency leads to abnormal neurite outgrowth and reduced glutamatergic synapses during development, suggesting abnormal neuronal maturation. Oxytocin stimulates the expression of numerous genes involved in neurite outgrowth and synapse formation in early development stages. Postnatal oxytocin administration has a strong effect on development that should be considered for certain neuropsychiatric conditions in infancy.

Keywords: Magel2; autism; development; oxytocin; synaptic proteins.

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References

REFERENCES

    1. Arastoo, M., Hacker, C., Popovics, P., Lucocq, J. M., & Stewart, A. J. (2016). Phospholipase C-η2 interacts with nuclear and cytoplasmic LIMK-1 during retinoic acid-stimulated neurite growth. Histochemistry and Cell Biology, 145(2), 163-173. https://doi.org/10.1007/s00418-015-1390-7
    1. Arsenault, J., Gholizadeh, S., Niibori, Y., Pacey, L. K., Halder, S. K., Koxhioni, E., Konno, A., Hirai, H., & Hampson, D. R. (2016). FMRP expression levels in mouse central nervous system neurons determine behavioral phenotype. Human Gene Therapy, 27(12), 982-996. https://doi.org/10.1089/hum.2016.090
    1. Ates, T., Oncul, M., Dilsiz, P., Topcu, I. C., Civas, C. C., Alp, M. I., Aklan, I., Ates Oz, E., Yavuz, Y., Yilmaz, B., Sayar Atasoy, N., & Atasoy, D. (2019). Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance. Neurobiology of Disease, 121, 58-64. https://doi.org/10.1016/j.nbd.2018.09.017
    1. Bakos, J., Bacova, Z., Grant, S. G., Castejon, A. M., & Ostatnikova, D. (2015). Are molecules involved in neuritogenesis and axon guidance related to autism pathogenesis? Neuromolecular Medicine, 17(3), 297-304. https://doi.org/10.1007/s12017-015-8357-7
    1. Bakos, J., Lestanova, Z., Strbak, V., Havranek, T., & Bacova, Z. (2014). Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat. Neuropeptides, 48(5), 281-286. https://doi.org/10.1016/j.npep.2014.06.004

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