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Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy in Drosophila
Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.ORCID-id: 0000-0003-2828-6891
Stockholms universitet, Naturvetenskapliga fakulteten, Zoologiska institutionen.ORCID-id: 0000-0002-1147-7766
2017 (engelsk)Inngår i: Frontiers in Cellular Neuroscience, E-ISSN 1662-5102, Vol. 11, artikkel-id 111Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The lifespan of Drosophila melanogaster can be extended substantially by inducing reproductive dormancy (also known as diapause) by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy. To study this we kept flies for seven or more weeks in normal rearing conditions or in diapause conditions and compared to 1-week-old flies in different behavioral assays of sleep, negative geotaxis and exploratory walking. We found that the senescence of geotaxis and locomotor behavior seen under normal rearing conditions was negligible in flies kept in dormancy. The normal senescence of rhythmic activity and sleep patterns during the daytime was also reduced by adult dormancy. Investigating the morphology of specific neuromuscular junctions (NMJs), we found that changes normally seen with aging do not take place in dormant flies. To monitor age-associated changes in neuronal circuits regulating activity rhythms, sleep and walking behavior we applied antisera to tyrosine hydroxylase (TH), serotonin and several neuropeptides to examine changes in expression levels and neuron morphology. In most neuron types the levels of stored neuromodulators decreased during normal aging, but not in diapause treated flies. No signs of neurodegeneration were seen in either condition. Our data suggest that age-related changes in motor neurons could be the cause of part of the behavioral senescence and that this is ameliorated by reproductive diapause. Earlier studies established a link between age-associated decreases in neuromodulator levels and behavioral decline that could be rescued by overexpression of neuromodulator. Thus, it is likely that the retained levels of neuromodulators in dormant flies alleviate behavioral senescence.

sted, utgiver, år, opplag, sider
2017. Vol. 11, artikkel-id 111
Emneord [en]
diapause, aging, sleep, negative geotaxis, walking behavior, insulin signaling, neuropeptides, dopamin
HSV kategori
Forskningsprogram
funktionell zoomorfologi
Identifikatorer
URN: urn:nbn:se:su:diva-156938DOI: 10.3389/fncel.2017.00111OAI: oai:DiVA.org:su-156938DiVA, id: diva2:1212981
Tilgjengelig fra: 2018-06-04 Laget: 2018-06-04 Sist oppdatert: 2023-02-22bibliografisk kontrollert
Inngår i avhandling
1. The role of insulin signaling during development, reproductive diapause and aging in Drosophila Melanogaster
Åpne denne publikasjonen i ny fane eller vindu >>The role of insulin signaling during development, reproductive diapause and aging in Drosophila Melanogaster
2018 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The insulin/insulin-like growth factor signaling pathway exists from invertebrates to vertebrates and it can regulate various biological processes, including development, metabolism, stress resistance and lifespan. In Drosophila, eight insulin-like peptides (DILP1-8) have been found. The specific function of each DILP is not fully known, especially for DILP1. In paper I, we found that dilp1 is specifically expressed in the brain insulin producing cells (IPCs), and it is mainly expressed from early pupa until few days of adult life, which correspond to non-feeding stages. The expression of dilp1 can last for at least 9 weeks of adult life when newborn virgin flies are induced to enter reproductive diapause. In addition, we found that the expression of dilp1 is under regulation by other dilps. Also larva-derived fat body, short neuropeptide F (sNPF) and juvenile hormone can affect dilp1 expression. We found that mutation of dilp1 affects female reproduction and starvation resistance. In paper II, we found that reproductive diapause can extend Drosophila life span, and at the same time ameliorate behavioral senescence, including negative geotaxis, activity rhythms and exploratory walking. Age-related changes in neuromuscular junction (NMJ) in abdominal muscle cannot be found in diapause-induced aging flies. The levels of several neuromodulators in the brain, including pigment dispersion factor (PDF), tyrosine hydroxylase (TH) and short neuropeptide F (sNPF), decreased significantly in normally aging flies, but less so in diapausing flies. In paper III, we show that mutation of dilp1 leads to a reduced organismal bodyweight, whereas overexpression increases it during the nonfeeding pupal stage. Overexpression of dilp1 additionally increases body size of flies, but reduces stores of larval-derived energy. This results in decreased starvation tolerance and increased feeding in newborn flies. In paper IV, we found that dilp1 expression is needed to extend lifespan in dilp2 mutant flies. Single dilp1 mutation has no effect on female lifespan, whereas transgene expression of dilp1 in flies with dilp1-dilp2 double mutant genetic background increased the lifespan. Furthermore, dilp1 and dilp2 interact to control circulating sugar, starvation resistance in a redundant or synergistic way.

sted, utgiver, år, opplag, sider
Stockholm: Department of Zoology, Stockholm University, 2018
Emneord
insulin-like peptides, reproductive diapause, behavioral senescence, neuromodulator, lifespan
HSV kategori
Forskningsprogram
funktionell zoomorfologi
Identifikatorer
urn:nbn:se:su:diva-159978 (URN)978-91-7797-431-4 (ISBN)978-91-7797-430-7 (ISBN)
Disputas
2018-11-02, Vivi Täckholmssalen (Q-salen), NPQ-huset, Svante Arrhenius Väg 20, Stockholm, 13:00 (engelsk)
Opponent
Veileder
Forskningsfinansiär
Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, VR: 621-2010-5742 and 2015-04626
Tilgjengelig fra: 2018-10-10 Laget: 2018-09-13 Sist oppdatert: 2022-02-26bibliografisk kontrollert

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