Effects of Statins on the Neurobiology of Learning and Memory Across the Lifespan

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DESCRIPTION (Provided by Applicant): The American Academy of Pediatrics has recently recommended the use of statins to treat high cholesterol in children. Currently, no studies have examined potential cognitive or neural effects of statins in healthy children or in juvenile animal models. To address this knowledge gap, the investigators will develop the songbird as a model system to test the influence of statins on learning, memory, and adult neurogenesis across the lifespan. They focus on cognitive processes occurring during the critical period for songbird vocal learning, an established model system for human speech acquisition. They will quantify and compare the cognitive and neural effects of statins using clinically-relevant doses of oral statins across juvenile development and in adulthood. Long-term and short-term memory will be assessed electrophysiologically in neurons of the avian auditory forebrain, and the accuracy of song learning will be quantified behaviorally. The investigators will delineate how rates of neuron production and survival across the lifespan contribute to vocal learning and memory in normal juvenile and adult brains. The locus and specificity of effects will be tested by comparing effects of hydrophilic and lipophilic statins, which differ in crossing the blood-brain barrier. They will provide a sensitive new methodology to test functional and structural effects of statins on the developing and adult brain. PROJECT NARRATIVE: The investigators will assess the longitudinal effects of oral statins on learning and memory across the lifespan. Negative effects on cognitive processes might be relevant to assessing the safety of long-term statin exposure, especially in children. Additionally, they will explore how rates of neuron production and survival across the lifespan contribute to learning and memory in normal brains. Data on neurogenesis and survival, in conjunction with functional consequences, will lead to new hypotheses about the role of the cholesterol synthesis pathway in critical aspects of neural development and plasticity.