stress-induced susceptibility to sudden cardiac death in mice with altered serotonin homeostasis应激对心脏性猝死在血清素水平改变了的小鼠体内平衡.pdf

Stress-Induced Susceptibility to Sudden Cardiac Death in Mice with Altered Serotonin Homeostasis 1 1 2 3 1 1 Luca Carnevali , Francesca Mastorci , Enrica Audero , Gallia Graiani , Stefano Rossi , Emilio Macchi , 4 5 6 3 2 Sergio Callegari , Alessandro Bartolomucci , Eugene Nalivaiko , Federico Quaini , Cornelius Gross , Andrea Sgoifo1* 1 Department of Evolutionary and Functional Biology, University of Parma, Italy, 2 Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy, 3 Department of Internal Medicine, University of Parma, Italy, 4 Division of Cardiology, Vaio Hospital, Fidenza (Parma), Italy, 5 Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, United States of America, 6 School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia Abstract In humans, chronic stressors have long been linked to cardiac morbidity. Altered serotonergic neurotransmission may represent a crucial pathophysiological mechanism mediating stress-induced cardiac disturbances. Here, we evaluated the physiological role of serotonin (5-HT) 1A receptors in the autonomic regulation of cardiac function under acute and chronic stress conditions, using 5-HT1A receptor knockout mice (KOs). When exposed to acute stressors, KO mice displayed a higher tachycardic stress response and a larger reduction of vagal modulation of heart rate than wild type counterparts (WTs). During a protocol of chronic psychosocial stress, 6 out of 22 (27%) KOs died from cardiac arrest. Close to death, they displayed a seve