Inhalation of marijuana affects Drosophila heart function

ABSTRACT We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for studying human diseases. Adult flies were exposed to marijuana for variable time periods and the effects on cardiac function were studied. Short treatment protocol incremented heart-rate variability. Contractility was augmented only under prolonged exposure to cannabis and it was associated with incremented calcium transient within cardiomyocytes. Neither the activity of the major proteins responsible for calcium handling nor the calcium load of the sarcoplasmic reticulum were affected by the cannabis treatment. The observed changes manifested in the cardiomyocytes even in the absence of the canonical cannabinoid receptors described in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster. By providing a simple and affordable platform prior to mammalian models, this characterization of cardiac function under marijuana exposure opens new paths for conducting genetic screenings using vaporized compounds. This article has an associated First Person interview with the first author of the paper. Summary: Marijuana induces early arrhythmogenesis and increases contractility in Drosophila. Our approach using this animal model allows us to carry out screenings to explore the impact of cannabinoids.

[1]  R. Kloner,et al.  Cardiovascular effects of marijuana. , 2019, Trends in cardiovascular medicine.

[2]  Heiko Meyer,et al.  SERCA is critical to control the Bowditch effect in the heart , 2018, Scientific Reports.

[3]  Yulan Xiong,et al.  Modeling Parkinson’s Disease in Drosophila: What Have We Learned for Dominant Traits? , 2018, Front. Neurol..

[4]  E. Portiansky,et al.  Drosophila melanogaster, an Emerging Animal Model for the Study of Human Cardiac Diseases , 2016 .

[5]  Paul M. L. Janssen,et al.  Myofilament Calcium Sensitivity: Role in Regulation of In vivo Cardiac Contraction and Relaxation , 2016, Front. Physiol..

[6]  Heiko Meyer,et al.  Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides , 2016, eLife.

[7]  N. Sonenberg,et al.  LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction , 2016, Nature Communications.

[8]  J. Hubbard,et al.  Cannabinoids: Medical implications , 2016, Annals of medicine.

[9]  M. Tayyab,et al.  GCMS analysis of Cannabis sativa L. from four different areas of Pakistan , 2015 .

[10]  A. Shevchenko,et al.  Endocannabinoids are conserved inhibitors of the Hedgehog pathway , 2015, Proceedings of the National Academy of Sciences.

[11]  A. Mattiazzi,et al.  Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster , 2014, PloS one.

[12]  R. Bodmer,et al.  Drosophila as a model to study the genetic mechanisms of obesity-associated heart dysfunction , 2012, Journal of cellular and molecular medicine.

[13]  Karla R. Kaun,et al.  Drosophila melanogaster as a model to study drug addiction , 2012, Human Genetics.

[14]  N. Bursac,et al.  A Method to Measure Myocardial Calcium Handling in Adult Drosophila , 2011, Circulation research.

[15]  C. Lotan,et al.  The potential for clinical use of cannabinoids in treatment of cardiovascular diseases. , 2011, Cardiovascular therapeutics.

[16]  R. Cooper,et al.  Roles of the Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Plasma Membrane Ca2+-ATPase and Na+/Ca2+ Exchanger in Regulation of Heart Rate in Larval Drosophila , 2010 .

[17]  M. Jimenez-Del-Rio,et al.  The cannabinoid CP55,940 prolongs survival and improves locomotor activity in Drosophila melanogaster against paraquat: Implications in Parkinson's disease , 2008, Neuroscience Research.

[18]  A. Paululat,et al.  Dynamics of heart differentiation, visualized utilizing heart enhancer elements of the Drosophila melanogaster bHLH transcription factor Hand. , 2006, Gene expression patterns : GEP.

[19]  M. Glass,et al.  Evolutionary origins of the endocannabinoid system. , 2006, Gene.

[20]  M. Glass,et al.  Cannabinoid receptors in invertebrates , 2006, Journal of evolutionary biology.

[21]  Joseph A Izatt,et al.  Drosophila as a model for the identification of genes causing adult human heart disease , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Chong,et al.  Correction , 2005, Emergency Medicine Journal.

[23]  M. Heisenberg,et al.  ISOGENIC AUTOSOMES TO BE APPLIED IN OPTIMAL SCREENING FOR NOVEL MUTANTS WITH VIABLE PHENOTYPES IN DROSOPHILA MELANOGASTER , 2005, Journal of neurogenetics.

[24]  M. Konsolaki,et al.  A model for studying Alzheimer's Aβ42-induced toxicity in Drosophila melanogaster , 2004, Molecular and Cellular Neuroscience.

[25]  R. Bijlsma,et al.  Changes in mortality patterns and temperature dependence of lifespan in Drosophila melanogaster caused by inbreeding , 2004, Heredity.

[26]  J. B. Duffy,et al.  GAL4 system in drosophila: A fly geneticist's swiss army knife , 2002, Genesis.

[27]  G. Stefano,et al.  The endocannabinoid system in invertebrates. , 2002, Prostaglandins, leukotrienes, and essential fatty acids.

[28]  M. Tanouye,et al.  Genetic suppression of seizure susceptibility in Drosophila. , 2001, Journal of neurophysiology.

[29]  M. Glass,et al.  Cannabinoid receptors are absent in insects , 2001, The Journal of comparative neurology.

[30]  D. Kosior,et al.  Paroxysmal atrial fibrillation following marijuana intoxication: a two-case report of possible association. , 2001, International journal of cardiology.

[31]  M. Elphick,et al.  The neurobiology and evolution of cannabinoid signalling. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  G. Singh,et al.  Atrial Fibrillation Associated with Marijuana Use , 2000, Pediatric Cardiology.

[33]  Donald M. Bers,et al.  Excitation-Contraction Coupling and Cardiac Contractile Force , 1991, Developments in Cardiovascular Medicine.

[34]  M. Awdeh,et al.  Marijuana and second-degree AV block. , 1981, Southern medical journal.

[35]  E. Domino,et al.  Some cardiovascular effects of marihuana smoking in normal volunteers , 1971, Clinical pharmacology and therapeutics.

[36]  A. Mattiazzi,et al.  Time course and mechanisms of phosphorylation of phospholamban residues in ischemia-reperfused rat hearts. Dissociation of phospholamban phosphorylation pathways. , 2002, Journal of molecular and cellular cardiology.

[37]  V A McKusick,et al.  On the naming of clinical disorders, with particular reference to eponyms. , 1998, Medicine.