Blue light (BL) is becoming increasingly prevalent in artificial illumination, raising concerns about its potential health hazard to humans. In fact, there is evidence suggesting that acute BL exposure may lead to oxidative stress and death of retinal cells specialized for photoreception. On the other hand, recent studies in Drosophila melanogaster demonstrated that chronic BL exposure across lifespan leads to accelerated aging manifested in reduced lifespan and brain neurodegeneration even in flies with genetically ablated eyes, suggesting that BL can damage cells and tissues not specialized for light perception. At the physiological level, BL exposure impairs mitochondria function in flies, but the metabolic underpinnings of these effects have not been studied. Here, we investigated effects of chronic BL on metabolic pathways in heads of eyes absent (eya ² ) mutant flies in order to focus on extra-retinal tissues. We compared metabolomic profiles in flies kept for 10 or 14 days in constant BL or constant darkness, using LC-MS and GC-MS. Data analysis revealed significant alterations in the levels of several metabolites suggesting that critical cellular pathways are impacted in BL-exposed flies. In particular, dramatic metabolic rearrangements are observed in heads of flies kept in BL for 14 days, including highly elevated levels of succinate but reduced levels of pyruvate and citrate, suggesting impairments in energy production. These flies also show onset of neurodegeneration and our analysis detected significantly reduced levels of several neurotransmitters including glutamate and Gamma-aminobutyric acid (GABA), suggesting that BL disrupts brain homeostasis. Taken together, these data provide novel insights into the mechanisms by which BL interferes with vital metabolic pathways that are conserved between fly and human cells.

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