Downregulation of the psychiatric susceptibility gene Cacna1c promotes mitochondrial resilience to oxidative stress in neuronal cells

Cell Death Discovery
Susanne MichelsC Culmsee

Abstract

Affective disorders such as major depression and bipolar disorder are among the most prevalent forms of mental illness and their etiologies involve complex interactions between genetic and environmental risk factors. Over the past ten years, several genome wide association studies (GWAS) have identified CACNA1C as one of the strongest genetic risk factors for the development of affective disorders. However, its role in disease pathogenesis is still largely unknown. Vulnerability to affective disorders also involves diverse environmental risk factors such as perinatal insults, childhood maltreatment, and other adverse pathophysiological or psychosocial life events. At the cellular level, such environmental influences may activate oxidative stress pathways, thereby altering neuronal plasticity and function. Mitochondria are the key organelles of energy metabolism and, further, highly important for the adaptation to oxidative stress. Accordingly, multiple lines of evidence including post-mortem brain and neuro-imaging studies suggest that psychiatric disorders are accompanied by mitochondrial dysfunction. In this study, we investigated the effects of Cacna1c downregulation in combination with glutamate-induced oxidative stress on ...Continue Reading

References

May 11, 1990·Proceedings of the National Academy of Sciences of the United States of America·B H Morimoto, D E Koshland
Jan 7, 1998·The Journal of Cell Biology·Y LiD Schubert
Mar 17, 2001·Bipolar Disorders·N A Levy, P G Janicak
Sep 10, 2004·American Journal of Physiology. Cell Physiology·Paul S BrookesShey-Shing Sheu
Nov 13, 2004·Current Psychiatry Reports·Kathleen Ries Merikangas, Nancy C P Low
Apr 9, 2008·Nature Chemical Biology·Andrea WilliamsDavid C Rubinsztein
Jun 7, 2008·Cell Death and Differentiation·S LandshamerC Culmsee
Aug 20, 2008·Nature Genetics·Manuel A R FerreiraUNKNOWN Wellcome Trust Case Control Consortium
Oct 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·G M CereghettiL Scorrano
Apr 11, 2009·Neuroscience·J H Barnett, J W Smoller
Feb 4, 2010·Journal of Psychiatric Research·Thomas FrodlEva M Meisenzahl
Jul 10, 2010·Circulation Research·Damodaran NarayananJonathan H Jaggar
Sep 8, 2010·Archives of General Psychiatry·Kristin L BigosDaniel R Weinberger
Sep 11, 2010·Progress in Neuro-psychopharmacology & Biological Psychiatry·Marta KuberaMichael Maes
Sep 18, 2010·Current Psychiatry Reports·Falk W Lohoff
Oct 4, 2011·Journal of Neuroscience Methods·S DiemertC Culmsee
Dec 27, 2011·Current Psychiatry Reports·Robert Keers, Rudolf Uher
Jan 3, 2012·Physiology & Behavior·Naresh KumarAmteshwar Singh Jaggi
Mar 16, 2012·The American Journal of Psychiatry·Valentina NanniAndrea Danese
Apr 19, 2012·Nature Reviews. Neuroscience·Husseini ManjiGuang Chen
Jun 6, 2012·Molecular Psychiatry·A S LeeAnjali M Rajadhyaksha
Jun 19, 2012·Progress in Neurobiology·Shambhu BhatTodd D Gould
Feb 23, 2013·The Journal of Biological Chemistry·Amalia M DolgaCarsten Culmsee
Mar 5, 2013·Lancet·UNKNOWN Cross-Disorder Group of the Psychiatric Genomics Consortium
May 23, 2013·Journal of Neurochemistry·Ana C AndreazzaLionel T Young
Aug 24, 2013·Frontiers in Physiology·Stephan M HuberFranziska Eckert
Mar 1, 2014·Cell and Tissue Research·Michael J Berridge
Dec 3, 2014·Cell Reports·Panos RoussosPamela Sklar
Feb 18, 2015·Nature Reviews. Neurology·Henrik HagbergPierre Gressens
Jul 27, 2015·Current Opinion in Neurobiology·Paul J Harrison
Sep 20, 2015·Progress in Neurobiology·Samuel HeyesAnnette C Dolphin

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Citations

Jul 15, 2020·International Journal of Molecular Sciences·Maria Victoria Niklison-ChirouGerry Melino
Jan 29, 2019·Frontiers in Psychiatry·Carsten CulmseeJudith Alferink
Nov 18, 2020·Biochemistry. Biokhimii︠a︡·G Melino
Apr 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Maria F NotermanEric B Taylor
May 15, 2021·Orphanet Journal of Rare Diseases·Miriam KessiFei Yin
Aug 26, 2021·The Journal of Cell Biology·Jörg IsenseeTim Hucho

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Methods Mentioned

BETA
transfection
lipidation
flow cytometry
pharmacotherapy
environmental stress
Protein Assay
Assay

Software Mentioned

Excel
WinSTAT

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