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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00483

Interaction of the psychiatric risk gene Cacna1c with post-weaning social isolation or environmental enrichment does not affect brain mitochondrial bioenergetics in rats

 Susanne Michels1, 2*,  Amalia M. Dolga3, Moria D. Braun2, 4, Theresa M. Kisko2, 4,  A Ö. Sungur2, 4, Stephanie H. Witt5,  Marcella Rietschel5,  Astrid Dempfle6,  Markus Wöhr2, 4,  Rainer K. Schwarting2, 4 and  Carsten Culmsee1, 2*
  • 1Institute of Pharmacology and Clinical Pharmacy, University of Marburg, Germany
  • 2Center for Mind, Brain and Behavior, University of Marburg, Germany
  • 3Department of Molecular Pharmacology, University of Groningen, Netherlands
  • 4Department of Experimental and Biological Psychology, University of Marburg, Germany
  • 5Department of Genetic Epidemiology in Psychiatry, Central Institute for Mental Health, Germany
  • 6Institute of Medical Informatics and Statistics, University of Kiel, Germany

The pathophysiology of neuropsychiatric disorders involves complex interactions between genetic and environmental risk factors. Confirmed by several genome-wide association studies, CACNA1C represents one of the most robustly replicated psychiatric risk genes. Besides genetic predispositions, environmental stress such as childhood maltreatment also contributes to enhanced disease vulnerability. Both, CACNA1C gene variants and stressful life events are associated with morphological alterations in the prefrontal cortex and the hippocampus. Emerging evidence suggests impaired mitochondrial bioenergetics as a possible underlying mechanism of these regional brain abnormalities. In the present study, we simulated the interaction of psychiatric disease-relevant genetic and environmental factors in rodents to investigate their potential effect on brain mitochondrial function using a constitutive heterozygous Cacna1c rat model in combination with a four-week exposure to either post-weaning social isolation, standard housing, or social and physical environmental enrichment. Mitochondria were isolated from the prefrontal cortex and the hippocampus to evaluate their bioenergetics, membrane potential, reactive oxygen species production, and respiratory chain complex protein levels. None of these parameters were considerably affected in this particular gene-environment setting. These negative results were very robust in all tested conditions demonstrating that Cacna1c depletion did not significantly translate into altered bioenergetic characteristics. Thus, further investigations are required to determine the disease-related effects on brain mitochondria.

Keywords: brain bioenergetics, Cav1.2 calcium channel, gene x environment interaction, Isolated mitochondria, neuropsychiatric disorders

Received: 23 Jan 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 Michels, Dolga, Braun, Kisko, Sungur, Witt, Rietschel, Dempfle, Wöhr, Schwarting and Culmsee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Ms. Susanne Michels, University of Marburg, Institute of Pharmacology and Clinical Pharmacy, Marburg, Germany, susanne.michels@pharmazie.uni-marburg.de
Prof. Carsten Culmsee, University of Marburg, Institute of Pharmacology and Clinical Pharmacy, Marburg, Germany, culmsee@staff.uni-marburg.de