TY - JOUR A1 - Gubert, Priscila A1 - Puntel, Bruna A1 - Lehmen, Tassia A1 - Fessel, Joshua P. A1 - Cheng, Pan A1 - Bornhorst, Julia A1 - Trindade, Lucas Siqueira A1 - Avila, Daiana S. A1 - Aschner, Michael A1 - Soares, Felix A. A. T1 - Metabolic effects of manganese in the nematode Caenorhabditis elegans through DAergic pathway and transcription factors activation JF - Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system N2 - Manganese (Mn) is an essential trace element for physiological functions since it acts as an enzymatic co-factor. Nevertheless, overexposure to Mn has been associated with a pathologic condition called manganism. Furthermore, Mn has been reported to affect lipid metabolism by mechanisms which have yet to be established. Herein, we used the nematode Caenorhabditis elegans to examine Mn’s effects on the dopaminergic (DAergic) system and determine which transcription factors that regulate with lipid metabolism are affected by it. Worms were exposed to Mn for four hours in the presence of bacteria and in a liquid medium (85 mM NaCl). Mn increased fat storage as evidenced both by Oil Red O accumulation and triglyceride levels. In addition, metabolic activity was reduced as a reflection of decreased oxygen consumption caused by Mn. Mn also affected feeding behavior as evidenced by decreased pharyngeal pumping rate. DAergic neurons viability were not altered by Mn, however the dopamine levels were significantly reduced following Mn exposure. Furthermore, the expression of sbp-1 transcription factor and let-363 protein kinase responsible for lipid accumulation control was increased and decreased, respectively, by Mn. Altogether, our data suggest that Mn increases the fat storage in C. elegans, secondary to DAergic system alterations, under the control of SBP-1 and LET-363 proteins. KW - Manganese KW - Caenorhabditis elegans KW - Lipid metabolism KW - Dopaminergic system KW - Manganism Y1 - 2018 U6 - https://doi.org/10.1016/j.neuro.2018.04.008 SN - 0161-813X SN - 1872-9711 VL - 67 SP - 65 EP - 72 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Gubert, Priscila A1 - Puntel, Bruna A1 - Lehmen, Tassia A1 - Bornhorst, Julia A1 - Avila, Daiana Silva A1 - Aschner, Michael A. A1 - Soares, Felix A. A. T1 - Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn′s effects on C. elegans reproduction and better understand the pathways related to these effects. Main methods. Young adult larval stage worms were treated for 4 h with Mn in 85 mM NaCl and Escherichia coli OP50 medium. Key findings. Mn reduced egg-production and egg-laying during the first 24 h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24 h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24 h. Significance Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation. KW - Manganese KW - Vitellogenin KW - Caenorhabditis elegans KW - DAF-16 transcription factor KW - Brood size Y1 - 2016 U6 - https://doi.org/10.1016/j.lfs.2016.03.016 SN - 0024-3205 SN - 1879-0631 VL - 151 SP - 218 EP - 223 PB - Elsevier CY - Oxford ER -