RUI: Peripheral Glucose Regulation Influences on Memory Modulation

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Lay SummaryMany drugs have been shown to enhance the cognitive processes that underlie learning and memory in laboratory animals and humans. Among the substances that have been implicated as memory modulators, several produce their beneficial effect by increasing glucose uptake and utilization in brain. Glucose is the major source of fuel for brain and acts as a substrate for the synthesis of several neurotransmitters. Epinephrine (EPI) is a vital component in the theory most often advanced in explaining how peripherally-acting memory modulators affect memory. According to one view, cognitive enhancing drugs act directly or indirectly upon the adrenal glands, which release EPI. Although EPI is peripherally acting and does not cross the blood-brain barrier, the release of EPI results in the subsequent release of glucose from liver. Increased amounts of glucose may enter brain and affect the neural systems underlying learning and memory. There is evidence, however, that some peripherally-acting cognitive enhancers act via a mechanism independent of glucose. One such substance is L-glucose. L-glucose is a peripherally acting glucose analog that does not cause an increase in blood-glucose levels. Furthermore, L-glucose enhances memory in rodents when injected peripherally but not when injected directly in brain. The experiments outlined in this proposal provide evidence of a mechanism that may be utilized by peripheral memory enhancer, L-glucose. The hypothesis is that L-glucose utilizes direct neural connections (liver to brain via the vagus nerve) as a way to affect the CNS and memory storage processes.