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Article

Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons

1
Department of Behavioral and Molecular Neurobiology, University of Regensburg, 93040 Regensburg, Germany
2
Department of Psychiatry and Psychotherapy, University of Regensburg, 93040 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2200; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062200
Received: 14 February 2020 / Revised: 16 March 2020 / Accepted: 20 March 2020 / Published: 23 March 2020
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
The neuropeptide oxytocin (OT) is a well-described modulator of socio-emotional traits, such as anxiety, stress, social behavior, and pair bonding. However, when dysregulated, it is associated with adverse psychiatric traits, such as various aspects of autism spectrum disorder (ASD). In this study, we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function. We provide evidence for MEF2A as the decisive factor defining the cellular response to OT: while OT induces neurite retraction in MEF2A expressing neurons, OT causes neurite outgrowth in absence of MEF2A. A CRISPR-Cas-mediated knockout of MEF2A and retransfection of an active version or permanently inactive mutant, respectively, validated our findings. We also identified the phosphatase calcineurin as the main upstream regulator of OT-induced MEF2A signaling. Further, MEF2A signaling dampens mitochondrial functioning in neurons, as MEF2A knockout cells show increased maximal cellular respiration, spare respiratory capacity, and total cellular ATP. In summary, we reveal a central role for OT-induced MEF2A activity as major regulator of cellular morphology as well as neuronal connectivity and mitochondrial functioning, with broad implications for a potential treatment of disorders based on morphological alterations or mitochondrial dysfunction. View Full-Text
Keywords: oxytocin; morphology; neurite outgrowth; neurite retraction; autism; MEF2A; CRISPR-Cas; hyperconnectivity oxytocin; morphology; neurite outgrowth; neurite retraction; autism; MEF2A; CRISPR-Cas; hyperconnectivity
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MDPI and ACS Style

Meyer, M.; Kuffner, K.; Winter, J.; Neumann, I.D.; Wetzel, C.H.; Jurek, B. Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons. Int. J. Mol. Sci. 2020, 21, 2200. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062200

AMA Style

Meyer M, Kuffner K, Winter J, Neumann ID, Wetzel CH, Jurek B. Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons. International Journal of Molecular Sciences. 2020; 21(6):2200. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062200

Chicago/Turabian Style

Meyer, Magdalena; Kuffner, Kerstin; Winter, Julia; Neumann, Inga D.; Wetzel, Christian H.; Jurek, Benjamin. 2020. "Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons" Int. J. Mol. Sci. 21, no. 6: 2200. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062200

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