- Title
- Stress-induced susceptibility to sudden cardiac death in mice with altered serotonin homeostasis
- Creator
- Carnevali, Luca; Mastorci, Francesca; Gross, Cornelius; Sgoifo, Andrea; Audero, Enrica; Graiani, Gallia; Rossi, Stefano; Macchi, Emilio; Callegari, Sergio; Bartolomucci, Alessandro; Nalivaiko, Eugene; Quaini, Federico
- Relation
- PLoS One Vol. 7, Issue 7
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0041184
- Publisher
- Public Library of Science
- Resource Type
- journal article
- Date
- 2012
- Description
- 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 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-HT1A 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.
- Subject
- stress; cardiac morbidity; serotonin; mice
- Identifier
- http://hdl.handle.net/1959.13/1050130
- Identifier
- uon:15119
- Identifier
- ISSN:1932-6203
- Language
- eng
- Full Text
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