Email updates

Keep up to date with the latest news and content from BMC Neuroscience and BioMed Central.

Open Access Highly Accessed Research article

Anaesthesia generates neuronal insulin resistance by inducing hypothermia

Christian Holscher2, Lidy van Aalten1 and Calum Sutherland1*

Author Affiliations

1 Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, Scotland, DD1 9SY, UK

2 School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland, UK

For all author emails, please log on.

BMC Neuroscience 2008, 9:100  doi:10.1186/1471-2202-9-100

Published: 9 October 2008

Abstract

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.

Conclusion

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.