Sleep and waking in mutant mice that do not express various proteins involved in serotonergic neurotransmission such as the serotonergic transporter, monoamine oxidase A, and 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT7 receptors

摘要: Sleep studies in knockout mice have investigated the effects on sleep and wakefulness of targeted disruption genes controlling various proteins involved serotonergic neurotransmission, particulary that regulate serotonin (5-hydroxytryptamine, 5-HT) concentration extracellular space: transporter (5-HTT) catabolytic enzyme, monoamine oxidase A (MAOA), as well receptors such 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C 5-HT7 sub-types. Mutant do not express 5-HTT, 5-HT1A or 5-HT1B exhibit larger amounts rapid eye movement (REM) than their wild-type counterparts. In case 5-HT1A-/- 5-HT1B-/- mice, phenotype is mimicked by pharmacological blockade receptors, respectively. This indicates no major compensatory mechanisms developed these mutants, REM under tonic inhibitory control via particularly sub-type. contrast, 5-HTT has opposite to those gene deletion. same manner, ablation (MAOA) results impairment sleep, whereas inhibition MAOA induces dramatic decrease. These might be related desensitization 5-HTT-/-, MAOA-/- but it seems essentially accounted for lack clearance from space during early life. Indeed, protection brain this overload life (by treatment with an inhibitor synthesis a receptor antagonist) rescues lasting 5-HTT-/- mice. contrast previous 5-HT7-/- reduced profile identical obtained rats after receptors. latter type mediate facilitation sleep. Finally, non-REM (NREM) affected mutations involving 5-HT2 Both 5-HT2A-/- 5-HT2C-/- mutants NREM compared change However, inactivation each effect genetic invalidation, i.e., enhancement pronounced Investigations response deprivation, total selective, immobilization stress indicate lost homeostatic properties, except enhanced rebound cortical slow wave activity deprivation. all constitutive examined tools, regulations reflect adaptations at other one mutation. adaptive processes participate addition mutation itself. To dissect more precisely role components regulations, data mutant need complemented using new molecular tools inducible lentiviral technology. Altogether, performed date demonstrated complex ofserotonin sleep-wakefulness when taking into account developmental components. sense, interesting help define “critical” periods vulnerability disorders probably parallel emotional impairments.