Sleep apneas are increased in mice lacking monoamine oxidase A.
OBJECTIVE
Alterations in the serotonin (5-HT) system have been suggested as a mechanism of sleep apnea in humans and rodents. The objective is to evaluate the contribution of 5-HT to this disorder.


METHODS
We studied sleep and breathing (whole-body plethysmography) in mutant mice that lack monoamine oxidase A (MAOA) and have increased concentrations of monoamines, including 5-HT.


RESULTS
Compared to wild-type mice, the mutants showed similar amounts of slow wave sleep (SWS) and rapid eye movement sleep (REMS), but exhibited a 3-fold increase in SWS and REMS apnea indices. Acute administration of the MAOA inhibitor clorgyline decreased REMS amounts and increased the apnea index in wild-type but not mutant mice. Parachlorophenylalanine, a 5-HT synthesis inhibitor, reduced whole brain concentrations of 5-HT in both strains, and induced a decrease in apnea index in mutant but not wild-type mice.


CONCLUSIONS
Our results show that MAOA deficiency is associated with increased sleep apnea in mice and suggest that an acute or chronic excess of 5-HT contributes to this phenotype.
Real
Caroline
C
Univ Paris-Sud, EA3544, Châtenay-Malabry Cedex, F-92296, Sérotonine et Neuropharmacologie, France. cprenat@noos.fr
Popa
Daniela
D
Seif
Isabelle
I
Callebert
Jacques
J
Launay
Jean-Marie
JM
Adrien
Joëlle
J
Escourrou
Pierre
P
D000818:Animals; D001921:Brain / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009474:Neurons / Q000201:enzymology; D010991:Plethysmography; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D012891:Sleep Apnea Syndromes / Q000201:enzymology*; D012894:Sleep Stages / Q000187:drug effects
D044263:Receptors, Serotonin, 5-HT1; D008995:Monoamine Oxidase; D003010:Clorgyline