Anaesthesia generates neuronal insulin resistance by inducing hypothermia.
BACKGROUND
Anaesthesia is commonly employed prior to surgical investigations and to permit icv injections in rodents. Indeed it is standard practise in many studies examining the subsequent actions of hormones and growth factors on the brain. Recent evidence that the basal activity of specific intracellular signalling proteins can be affected by anaesthesia prompted us to examine the effect of anaesthesia not only on the basal activity but also the insulin sensitivity of the major insulin signalling pathways.


RESULTS
We find that urethane- and ketamine-induced anaesthesia results in rapid activation of the phosphatidylinositol (PI) 3-kinase-protein kinase B (PKB) signalling pathway in the brain, increases tau phosphorylation while at the same time reducing basal activity of the Ras-ERK pathway. Subsequent injection of insulin does not alter the activity of either the PI 3-kinase or ERK signalling pathways, indicating a degree of neuronal molecular insulin resistance. However, if body temperature is maintained during anaesthesia then there is no alteration in the basal activity of these signalling molecules. Subsequent response of both pathways to insulin injection is restored.


CONCLUSIONS
The data is consistent with a hypothermia related alteration in neuronal signalling following anaesthesia, and emphasises the importance of maintaining the body temperature of rodents when monitoring insulin (or growth factor/neurotrophic agent) action in the brain of anesthetised rodents.
Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland, DD1 9SY, UK. c.holscher@ulster.ac.uk
Christian
C
Holscher
Lidy
L
van Aalten
Calum
C
Sutherland
D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007036:Hypothermia, Induced; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014520:Urethane / Q000494:pharmacology; D014991:Xylazine / Q000494:pharmacology; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism
D000777:Anesthetics; D007328:Insulin; D016875:tau Proteins; D014991:Xylazine; D014520:Urethane; D007649:Ketamine; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3