Analysis of uncoupling protein 2-deficient mice upon anaesthesia and sedation revealed a role for UCP2 in locomotion.
General anaesthesia is associated with hypothermia, oxidative stress, and immune depression. Uncoupling Protein (UCP2) is a member of the mitochondrial carrier family present in many organs including the spleen, the lung and the brain. A role of UCP2 in the activation of the inflammatory/immune cells, in the secretion of hormones, and in the excitability of neurons by regulating the production of reactive oxygen species has been discussed. Because of the side effects of anaesthesia listed above, we aimed to question the expression and the function of UCP2 during anaesthesia. Induction of anaesthesia with ketamine (20 mg/kg) or isoflurane (3.6%) and induction of sedation with the α2 adrenergic receptor agonist medetomidine (0.2 mg/kg) stimulated infiltration of immune cells in the lung and increased UCP2 protein content in the lung, in both immune and non-immune cells. UCP2 content in the lung inversely correlated with body temperature decrease induced by medetomidine treatment. Challenge of the Ucp2(-/-) mice with isoflurane and medetomidine revealed an earlier behavioral recovery phenotype. Transponder analysis of body temperature and activity showed no difference between Ucp2(-/-) and control mice in basal conditions. However, upon an acute decrease of body temperature induced by medetomidine, Ucp2(-/-) mice exhibited increased locomotion activity. Together, these results show that UCP2 is rapidly mobilized during anaesthesia and sedation in immune cells, and suggest a role of UCP2 in locomotion.
INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France.
Marie-Clotilde
MC
Alves-Guerra
Caroline
C
Aheng
Claire
C
Pecqueur
Sandrine
S
Masscheleyn
Pierre Louis
PL
Tharaux
Anne
A
Druilhe
Daniel
D
Ricquier
Etienne
E
Challet
Bruno
B
Miroux
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000758:Anesthesia; D000762:Anesthesia Recovery Period; D000818:Animals; D001831:Body Temperature / Q000235:genetics; D015870:Gene Expression; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D008124:Locomotion / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000071246:Uncoupling Protein 2
D018712:Analgesics, Non-Narcotic; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D020926:Medetomidine