| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Research Abstract |
Although it is widely known that aging is associated with memory loss, the specific molecular mechanisms that contribute to age-related memory impairment (AMI) are unknown, because of a lack of AMI-specific mutants. Previously, we determined that Drosophila aging specifically impairs memory phase depending on amnesiac (amn), gene encoding putative neuropeptides, and hypothesized that signaling downstream of amn leads to AMI. In this current project, we extend this work by screening for mutants with altered AMI onset and identifying that heterozygous mutations in DC0, the gene encoding the catalytic subunit of PKA, delay AMI more than two fold without affecting memory at young ages. Furthermore, our identified DC0 mutants do not show any increases in longevity, demonstrating that AMI can be dissociated from organismal aging. Given the identification of DC0, we demonstrate that PKA activity in the mushroom bodies (MBs), structures important in memory formation, causes AMI and AMI onset can be controlled by altering cAMP/PKA signaling activity in the MBs. Notably, putative neuropeptides encoded by amn are proposed to regulate cAMP level, and DPM cells expressing amn innervate MBs. In addition, amn mutants do not show further memory decay upon aging. We show here that both amn-dependent memory and AMI are restored in amn ; DC0/+ double mutants. These results suggest that cAMP/PKA signaling in the MBs is a downstream of amn and leads to AMI upon aging.
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