title: Glial dysfunction causes age-related memory impairment in Drosophila.
abstract: Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamazaki
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Junjiro
authors.initials: J
authors.lastname: Horiuchi
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Saeki
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Motomi
authors.initials: M
authors.lastname: Matsuno
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Naganos
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Institute of Advanced Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Taoka
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-osawa, Hachioji, Tokyo 192-0397, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo 156-8506, Japan. Electronic address: saitoe-mn@igakuken.or.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Saitoe
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D003214:Conditioning, Classical / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism*; D011766:Pyruvate Carboxylase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D011766:Pyruvate Carboxylase