Date of Award
Bachelor of Science
Ewan C. McNay, Ph.D.
Paolo E. Forni, Ph.D.
Insulin is a peptide hormone released by beta pancreatic cells . Insulin’s best-known function is to regulate absorption of glucose into peripheral tissue: this occurs via activation of the phosphoinositide 3-kinase (PI3K) signaling cascade and subsequent translocation of glucose transporter 4 (GLUT4) to the cell surface. This canonical peripheral insulin signaling pathway appears to exist in essentially identical form within the central nervous system (CNS), so that insulin promotes entry of glucose into neural cells and subsequent increased metabolism. In order to maintain proper function, insulin-responsive hippocampal neurons and glia require glucose metabolism; a catabolic energy-yielding process that requires insulin signaling to provide glucose. In vivo microdialysis studies have shown difficulty-correlated depletion of hippocampal extracellular fluid (ECF) glucose concentration during a cognitively-demanding task, indicating that the hippocampus not only depends on glucose metabolism for proper function but regularly functions under conditions of suboptimal supply. We hypothesized that blockade of insulin signaling might attenuate glucose-induced hippocampal cognitive enhancement via disruption of the insulin signaling pathway, preventing the entry of additional glucose via GLUT4. The present study aimed to investigate insulin’s role as a mediator of the enhancement of spatial working memory by exogenous glucose in vivo. Unexpectedly, unilateral intrahippocampal administration of supraphysiological glucose in a novel, larger microinjection volume significantly impaired spatial working memory. Our data also suggest that within the hippocampus, insulin signaling may possibly work through alternative substrates, such as insulin-like growth factors I or II. Administration of supraphysiological glucose resulted in no significant effect on hippocampal function, suggesting that unilateral administration may be insufficient to enhance hippocampal function. Our results also suggest glucose-induced improvement of hippocampal function may work in a dose-dependent manner in the hippocampus. These unexpected findings contribute to the knowledge of glucose-induced hippocampal enhancement and its relation to proper insulin signaling.
Carter, Jeremy, "Investigating the Effects of Intrahippocampal Glucose Administration on Spatial Working Memory in Rats" (2019). Biological Sciences. 57.