title: Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors.
abstract: Multiple neurological disorders are characterized by the abnormal accumulation of protein aggregates and the progressive impairment of complex behaviors. Our Drosophila studies demonstrate that middle-aged wild-type flies (WT, ~4-weeks) exhibit a marked accumulation of neural aggregates that is commensurate with the decline of the autophagy pathway. However, enhancing autophagy via neuronal over-expression of Atg8a (Atg8a-OE) reduces the age-dependent accumulation of aggregates. Here we assess basal locomotor activity profiles for single- and group-housed male and female WT flies and observed that only modest behavioral changes occurred by 4-weeks of age, with the noted exception of group-housed male flies. Male flies in same-sex social groups exhibit a progressive increase in nighttime activity. Infrared videos show aged group-housed males (4-weeks) are engaged in extensive bouts of courtship during periods of darkness, which is partly repressed during lighted conditions. Together, these nighttime courtship behaviors were nearly absent in young WT flies and aged Atg8a-OE flies. Previous studies have indicated a regulatory role for olfaction in male courtship partner choice. Coincidently, the mRNA expression profiles of several olfactory genes decline with age in WT flies; however, they are maintained in age-matched Atg8a-OE flies. Together, these results suggest that middle-aged male flies develop impairments in olfaction, which could contribute to the dysregulation of courtship behaviors during dark time periods. Combined, our results demonstrate that as Drosophila age, they develop early behavior defects that are coordinate with protein aggregate accumulation in the nervous system. In addition, the nighttime activity behavior is preserved when neuronal autophagy is maintained (Atg8a-OE flies). Thus, environmental or genetic factors that modify autophagic capacity could have a positive impact on neuronal aging and complex behaviors.
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Ratliff
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Mauntz
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Roxanne W
authors.initials: RW
authors.lastname: Kotzebue
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Arysa
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Achal
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Ayeh
authors.initials: A
authors.lastname: Barekat
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America.
authors.forename: Kaelyn A
authors.initials: KA
authors.lastname: Finley
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Sparhawk
authors.affiliation: Departments of Neurosciences and Pharmacology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America; Department of Pharmacology, National University of Singapore, Singapore, Singapore.
authors.forename: Deron R
authors.initials: DR
authors.lastname: Herr
authors.affiliation: Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Harris
authors.affiliation: Departments of Neurosciences and Pharmacology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.affiliation: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America; Expression Drug Designs, LLC, San Diego, California, United States of America; Department of Biology, San Diego State University, San Diego, California, United States of America.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Finley
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D003380:Courtship; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D066329:Protein Aggregates; D012737:Sex Factors; D012903:Smell / Q000235:genetics*
chemical_list: C527373:Atg8a protein, Drosophila; D029721:Drosophila Proteins; D066329:Protein Aggregates; D020962:Heterotrimeric GTP-Binding Proteins