title: Disruption of dopamine homeostasis has sexually dimorphic effects on senescence characteristics of Drosophila melanogaster.
abstract: The neurotransmitter dopamine (DA) is known to be involved in a multitude of physiological processes. We investigated sexually dimorphic effects of disruptions in DA homeostasis and its relationship to senescence using three different Drosophila melanogaster mutants namely Catsup (Catsup26) with elevated DA levels, and pale (ple2), Punch (PuZ22) with depleted DA levels. In all genotypes including controls, DA levels were significantly lower in old (45-50-day-old) flies compared with young (3-5-day-old) in both sexes. Interestingly, females had lower DA content than males at young age whereas this difference was not observed in old age, suggesting that males had a larger decline in DA levels with age. Females, in general, were longer lived compared with males in all genotypes except ple2mutants with depleted DA levels. This phenotype was abolished in the ple2rescue flies. Interestingly, females also demonstrated marked age-related decline in circadian locomotor activity compared with males. Old Catsup26males with elevated DA levels accumulated significantly lower levels of lipid peroxidation product 4-hydroxy 2-nonenal (4-HNE) compared with age-matched wild type, ple2and PuZ22mutant males. In Catsup26revertant lines this phenomenon was absent. We also observed a sexually dimorphic response in the expression levels of key stress and aging associated and/or related transcription factor genes across genotypes with elevated or depleted DA levels which was reverted to wild type levels in specific rescue lines. Taken together, our results reveal a novel sexually dimorphic involvement of DA in senescence characteristics of D. melanogaster.
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS, 39762, USA.|Institute of Entomology, Biology Centre, Academy of Sciences, České Budĕjovice, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bednářová
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS, 39762, USA.
authors.forename: Marley E
authors.initials: ME
authors.lastname: Hanna
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kuntol
authors.initials: K
authors.lastname: Rakshit
authors.affiliation: Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: O'Donnell
authors.affiliation: Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS, 39762, USA.
authors.forename: Natraj
authors.identifier: 0000-0001-6832-259X
authors.initials: N
authors.lastname: Krishnan
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D057906:Circadian Clocks; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D005838:Genotype; D006706:Homeostasis; D015227:Lipid Peroxidation; D008124:Locomotion; D008297:Male; D012737:Sex Factors
chemical_list: D029721:Drosophila Proteins; C511455:catsup protein, Drosophila; D004298:Dopamine
keywords: 4-hydroxynonenal; aging; circadian rhythms; lifespan; protein carbonyl