Disruption of dopamine homeostasis has sexually dimorphic effects on senescence characteristics of Drosophila melanogaster. (7th February 2017)

• Record Type: Journal Article
• Authors: Bednářová, Andrea; Hanna, Marley E.; Rakshit, Kuntol; O'Donnell, Janis M.; Krishnan, Natraj
• Editors: Galizia, C. Giovanni
• Is Part Of: European journal of neuroscience. Volume 45:Number 6(2017)
• Page Start: 816
• Page End: 825
• Publication Date: 2017-02-07
• Subjects: 4‐hydroxynonenal -- aging -- circadian rhythms -- lifespan -- protein carbonyl; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13525
• Languages: English
• ISSNs: 0953-816X

Abstract

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 ( Catsup 26 ) with elevated DA levels, and pale ( ple 2 ), Punch ( Pu Z22 ) 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 ple 2 mutants with depleted DA levels. This phenotype was abolished in the ple 2 rescue flies. Interestingly, females also demonstrated marked age‐related decline in circadian locomotor activity compared with males. Old Catsup 26 males with elevated DA levels accumulated significantly lower levels of lipid peroxidation product 4‐hydroxy 2‐nonenal (4‐HNE) compared with age‐matched wild type, ple 2 and Pu Z22 mutant males. In Catsup 26 revertant 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 . Abstract : Sexually dimorphic effects of disruptions in dopamine (DA) homeostasis and its relationship to senescence were investigated in Drosophila melanogaster . Catsup 26 with elevated DA levels, and ple 2 and Pu Z22 with depleted DA levels showed sex‐specific effects in longevity, activity, senescence, and age‐associated transcription factors. These results reveal a novel sexually dimorphic involvement of DA in senescence characteristics of D. melanogaster .