Article abstract
Nature Neuroscience 10, 478 - 484 (2007)
Published online: 25 February 2007 | doi:10.1038/nn1863
The Drosophila DCO mutation suppresses age-related memory impairment without affecting lifespan
Daisuke Yamazaki1,2,5, Junjiro Horiuchi1,5, Yasuko Nakagami1,3, Shintaro Nagano1,2, Takuya Tamura1,4 & Minoru Saitoe1
Abstract
The study of age-related memory impairment (AMI) has been hindered by a lack of AMI-specific mutants. In a screen for such mutants in Drosophila melanogaster, we found that heterozygous mutations of DCO (DCO/+), which encodes the major catalytic subunit of cAMP-dependent protein kinase (PKA), delay AMI more than twofold without affecting lifespan or memory at early ages. AMI is restored when a DCO transgene is expressed in mushroom bodies, structures important for olfactory memory formation. Furthermore, increasing cAMP and PKA activity in mushroom bodies causes premature AMI, whereas reducing activity suppresses AMI. In Drosophila AMI consists of a specific reduction in memory dependent on the amnesiac (amn) gene. amn encodes putative neuropeptides that have been proposed to regulate cAMP levels in mushroom bodies. Notably, both the memory and AMI defects of amn mutants are restored in amn;DCO/+ double mutants, suggesting that AMI is caused by an age-related disruption of amn-dependent memory via PKA activity in mushroom bodies.
- Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
- Department of Biological Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
- Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
- These authors contributed equally to this work.
Correspondence to: Minoru Saitoe1 e-mail: saitoe@tmin.ac.jp
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