title: Stress-induced susceptibility to sudden cardiac death in mice with altered serotonin homeostasis.
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-HT(1A) 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 severe bradycardia, a lengthening of cardiac interval (P wave, PQ and QRS) duration, a notched QRS complex and a profound hypothermia. In the same period, the remaining knockouts exhibited higher values of heart rate than WTs during both light and dark phases of the diurnal rhythm. At sacrifice, KO mice showed a larger expression of cardiac muscarinic receptors (M2), whereas they did not differ for gross cardiac anatomy and the amount of myocardial fibrosis compared to WTs. This study demonstrates that chronic genetic loss of 5-HT(1A) receptors is detrimental for cardiovascular health, by intensifying acute, stress-induced heart rate rises and increasing the susceptibility to sudden cardiac death in mice undergoing chronic stress.
authors: Department of Evolutionary and Functional Biology, University of Parma, Italy.
authors: Luca
authors: L
authors: Carnevali
authors: Francesca
authors: F
authors: Mastorci
authors: Enrica
authors: E
authors: Audero
authors: Gallia
authors: G
authors: Graiani
authors: Stefano
authors: S
authors: Rossi
authors: Emilio
authors: E
authors: Macchi
authors: Sergio
authors: S
authors: Callegari
authors: Alessandro
authors: A
authors: Bartolomucci
authors: Eugene
authors: E
authors: Nalivaiko
authors: Federico
authors: F
authors: Quaini
authors: Cornelius
authors: C
authors: Gross
authors: Andrea
authors: A
authors: Sgoifo
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001919:Bradycardia / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004562:Electrocardiography / Q000379:methods; D004594:Electrophysiology / Q000379:methods; D005355:Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015233:Models, Statistical; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism; D012919:Social Behavior; D013315:Stress, Psychological; D013997:Time Factors
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin