title: Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.
abstract: Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.
authors: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; PRESTO, Japan Science and Technology Agency (JST), Gobancho, Chiyoda-ku, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Gobancho, Chiyoda-ku, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Chihara
authors: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors: Aki
authors: A
authors: Kitabayashi
authors: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors: Michie
authors: M
authors: Morimoto
authors: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
authors: Ken-ichi
authors: K
authors: Takeuchi
authors: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Kaoru
authors: K
authors: Masuyama
authors: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, Florida, United States of America; Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
authors: Ayako
authors: A
authors: Tonoki
authors: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, Florida, United States of America.
authors: Ronald L
authors: RL
authors: Davis
authors: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Jing W
authors: JW
authors: Wang
authors: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; CREST, Japan Science and Technology Agency (JST), Gobancho, Chiyoda-ku, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Miura
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000502:physiology; D001931:Brain Mapping; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics*; D002633:Chemotaxis / Q000235:genetics*; D003712:Dendrites / Q000187:drug effects / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D027845:Malus; D018034:Olfactory Receptor Neurons; D018035:Receptors, Odorant; D012903:Smell / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000600052:Or42b protein, Drosophila; C000600051:Or92a protein, Drosophila; D018035:Receptors, Odorant; D053148:Caspase 3