Insulin promotes LTP in mice by switching the energy substrate preference of astrocytes to fatty acids [Rattus]

A total of 37,185 transcripts were detected from RNA extracts from primary cultured astrocytes, and neurons isolated from Rattus hippocampus. After exposing astrocytes to insulin (200 nM) for 6h, 883 transcripts were upregulated 2SD or greater and 852 transcripts were downregulated 2SD or greater compared with vehicle treated control astrocyte cultures. This general pattern of gene expression was maintained for at least 12h in astrocytes where the expression of 811 genes were increased and 849 genes decreased compared with vehicle treated astrocytes. Informatic interrogation of genes with expression greater or less than 2 SD at the 6h and 12h time points in astrocytes identified signaling pathways associated with fatty acid activation, fatty acid ß-oxidation, cAMP, gap junction, dendritic cell maturation ceramide degradation, triacylglycerol degradation and phospholipase activation. The functional association of gene changes in astrocytes after treatment with insulin for 6 and 12 h were almost exclusively related to the synthesis and storage of diacylglycerides, sterols, and other lipids. After exposing primary cultured Rattus hippocampal neurons to insulin (200 nM) for 6h, 753 genes were upregulated and 660 genes downregulated. This general pattern of gene expression was maintained for at least 12h when 768 genes were upregulated versus 736 genes downregulated in insulin treated neurons. Changes in gene expression profiles of neurons exposed to insulin for 6h, and 12h identified signaling pathways associated with actin-based motility, tight junctions, dendritic cell maturation, serotonin receptor, CREB (cAMP-response element binding protein), and axonal guidance. The functional association of gene changes in neurons after treatment with insulin for 6h, and 12h were largely related to neuroprotective/neurotrophic effects including tyrosine kinase tec-1 activation, synaptogenesis activation, and regulation of actin based cytoskeleton activation by the Rho family GTPases. These data suggest that insulin regulates neurotrophic signaling/functions in neurons and primary regulates lipid metabolism associated with fatty acid oxidation in astrocytes. Overall design: Effect of Insulin exposure in the regulation of lipid metabolism in the brain. There are two cell types, astrocytes and neurons. For each cell type one sample was treated with insulin for either 6hours, or 12hours and compared to a control of 0minutes treatment, for a total of six samples.