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Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity

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Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. / Bianchini, Matheus C.; Gularte, Claudia Ortiz Alves; Nogara, Pablo A.; Krum, Barbara N.; Gayer, Mateus C.; Bridi, Jessika C.; Roos, Daniel H.; Roehrs, Rafael; Fachinetto, Roselei; Pinton, Simone; Avila, Daiana S.; Hirth, Frank; Rocha, João B.T.; Puntel, Robson L.

In: Metallomics, Vol. 11, No. 2, 01.02.2019, p. 362-374.

Research output: Contribution to journalArticle

Harvard

Bianchini, MC, Gularte, COA, Nogara, PA, Krum, BN, Gayer, MC, Bridi, JC, Roos, DH, Roehrs, R, Fachinetto, R, Pinton, S, Avila, DS, Hirth, F, Rocha, JBT & Puntel, RL 2019, 'Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity', Metallomics, vol. 11, no. 2, pp. 362-374. https://doi.org/10.1039/c8mt00268a

APA

Bianchini, M. C., Gularte, C. O. A., Nogara, P. A., Krum, B. N., Gayer, M. C., Bridi, J. C., Roos, D. H., Roehrs, R., Fachinetto, R., Pinton, S., Avila, D. S., Hirth, F., Rocha, J. B. T., & Puntel, R. L. (2019). Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. Metallomics, 11(2), 362-374. https://doi.org/10.1039/c8mt00268a

Vancouver

Bianchini MC, Gularte COA, Nogara PA, Krum BN, Gayer MC, Bridi JC et al. Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. Metallomics. 2019 Feb 1;11(2):362-374. https://doi.org/10.1039/c8mt00268a

Author

Bianchini, Matheus C. ; Gularte, Claudia Ortiz Alves ; Nogara, Pablo A. ; Krum, Barbara N. ; Gayer, Mateus C. ; Bridi, Jessika C. ; Roos, Daniel H. ; Roehrs, Rafael ; Fachinetto, Roselei ; Pinton, Simone ; Avila, Daiana S. ; Hirth, Frank ; Rocha, João B.T. ; Puntel, Robson L. / Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. In: Metallomics. 2019 ; Vol. 11, No. 2. pp. 362-374.

Bibtex Download

@article{5982203ef26442d087c88188f58e29fb,
title = "Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity",
abstract = "{\textcopyright} The Royal Society of Chemistry. Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 μM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity.",
author = "Bianchini, {Matheus C.} and Gularte, {Claudia Ortiz Alves} and Nogara, {Pablo A.} and Krum, {Barbara N.} and Gayer, {Mateus C.} and Bridi, {Jessika C.} and Roos, {Daniel H.} and Rafael Roehrs and Roselei Fachinetto and Simone Pinton and Avila, {Daiana S.} and Frank Hirth and Rocha, {Jo{\~a}o B.T.} and Puntel, {Robson L.}",
year = "2019",
month = feb,
day = "1",
doi = "10.1039/c8mt00268a",
language = "English",
volume = "11",
pages = "362--374",
journal = "Metallomics",
issn = "1756-5901",
publisher = "Royal Society of Chemistry",
number = "2",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity

AU - Bianchini, Matheus C.

AU - Gularte, Claudia Ortiz Alves

AU - Nogara, Pablo A.

AU - Krum, Barbara N.

AU - Gayer, Mateus C.

AU - Bridi, Jessika C.

AU - Roos, Daniel H.

AU - Roehrs, Rafael

AU - Fachinetto, Roselei

AU - Pinton, Simone

AU - Avila, Daiana S.

AU - Hirth, Frank

AU - Rocha, João B.T.

AU - Puntel, Robson L.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - © The Royal Society of Chemistry. Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 μM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity.

AB - © The Royal Society of Chemistry. Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 μM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity.

UR - http://www.scopus.com/inward/record.url?scp=85061845516&partnerID=8YFLogxK

U2 - 10.1039/c8mt00268a

DO - 10.1039/c8mt00268a

M3 - Article

C2 - 30516209

AN - SCOPUS:85061845516

VL - 11

SP - 362

EP - 374

JO - Metallomics

JF - Metallomics

SN - 1756-5901

IS - 2

ER -

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