＜Symposium I＞Genetic dissection of age-related memory impairment in Drosophila

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  • Genetic dissection of age related memory impairment in Drosophila

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Age-related memory impairment （AMI） is an important phenotype of brain aging. Understanding the molecular mechanisms underlying AMI is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to developing drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecifi c decay of memory processes that results from dysfunction of neural networks. However, extensive behavioral genetic characterization of AMI with Drosophila demonstrated that AMI results from disruption in specifi c memory process. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory （STM）, middle-term memory （MTM）, and longer-lasting anesthesia-resistant memory （ARM）. Significantly, AMI results from the specific decay of only one memory component, amn-dependent MTM, and not other components. Since amnesiac encodes peptides that regulate adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a fi nding consistent with several models of AMI in mammals. In fact, hypomorphic mutations in PKA catalytic subunit signifi cantly suppress AMI. As cAMP signaling is an essential signaling for learning and memory, these studies suggest antagonistic pleiotropic eff ect of cAMP signaling. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.

弘前医学. 61(Suppl.), 2010, p.S26-S33

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  • 弘前医学

    弘前医学 61 (Supplement), S26-S33, 2010-07-08

    弘前大学大学院医学研究科・弘前医学会

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