Reducing Glut2 throughout the body does not result in cognitive behaviour differences in aged male mice
- PDF / 924,325 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 41 Downloads / 157 Views
BMC Research Notes Open Access
RESEARCH NOTE
Reducing Glut2 throughout the body does not result in cognitive behaviour differences in aged male mice Nicola Morrice1, Lidy van Aalten1, Alison McNeilly2, Rory J. McCrimmon2, Ewan R. Pearson3, Rosamund Langston2 and Calum Sutherland1*
Abstract Objectives: GLUT2 is a major facilitative glucose transporter, expressed from the SLC2A2 gene, with essential roles in the liver. Recent work in mice has shown that preventing Glut2 production in specific neuronal populations increases sugar-seeking behaviour, highlighting the importance of Slc2a2 gene expression in the brain. It implies that reduced GLUT2 in the brain, due to genetic polymorphisms or disease, impacts health through behaviour change. Defects in glucose transport in the brain are observed in conditions including type-2 diabetes and dementia. Few studies have directly examined the effect of modulating neuronal glucose transporter expression on cognitive function. The aim of this study was to investigate whether inactivating one Slc2a2 allele throughout the body had major effects on cognition. Cognitive tests to assess recognition memory, spatial working memory and anxiety were performed in Slc2a2 whole-body heterozygous mice (i.e. reduced Glut2 mRNA and protein), alongside littermates expressing normal levels of the transporter. Results: No significant effects on neurological functions and cognitive capabilities were observed in mice lacking one Slc2a2 allele when fed a chow diet. This suggests that the minor variations in GLUT2 levels that occur in the human population are unlikely to influence behaviour and basic cognition. Keyword: Glucose, GWAS, Diabetes, GLUT2, Neuronal function Introduction Maintenance of glucose homeostasis is essential for survival and this is dependent on the action of cellular glucose transporters [1–5]. A major class of glucose transporters are the GLUT (glucose transporter) family, which transport glucose across the plasma membrane via facilitative diffusion [6]. GLUT2, a low affinity, high occupancy family member, is the major glucose transporter in the liver, where it is required for appropriate glucose uptake by hepatocytes, while in mice Glut2 also has an *Correspondence: [email protected] 1 Division of Cellular Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, James Arnott Drive, Dundee DD1 9SY, UK Full list of author information is available at the end of the article
essential role in glucose-stimulated insulin secretion in the pancreas [6, 7]. Mutations in the human SLC2A2 gene (which encodes for GLUT2 protein) cause Fanconi-Bickel syndrome (hepatomegaly and renal disease) and have been rarely found as a cause of neonatal diabetes. Genome-wide association studies indicate that SLC2A2 sequence variation associates with risk of fasting hyperglycaemia, progression to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. We previously showed that single nucleotide polymorphisms (SNPs) found at the SLC2A2 locus, th
Data Loading...
