TY - JOUR
T1 - Motor dysfunction in
Drosophila melanogaster as a biomarker for developmental neurotoxicity.
AU - Cabrita, Ana
AU - Medeiros, Alexandra M
AU - Pereira, Telmo
AU - Rodrigues, António Sebastião
AU - Kranendonk, Michel
AU - Mendes, César S
N1 - Funding: We thank Matthew Scott and Jun Zhang for the Rab3:YFP plasmid, John Tuthill for suggesting the R22A08 driver, Mendes lab, Rita Teodoro and her lab for comments and suggestions during the execution of this project, Allan Mancoo for assistance in the design of the PCA script, Daniela Pereira and Edgar Gomes for ll OPEN ACCESS iScience 25, 104541, July 15, 2022 15 iScience Article comments on the manuscript. We thank the scientific and technical assistance from the Microscopy and Fly facilities. We also thank CONGENTO: consortium for genetically tractable organisms and the Bloomington Drosophila Stock Center for fly stocks. This work was supported by H2020 Marie Skłodowska-Curie Actions (H2020-MSCA-IF-2016, #752891, GEMiNI to CSM), Fundac¸ a˜ o para a Cieˆ ncia e a Tecnologia (FCT) (PTDC/ BIA-COM/0151/2020, iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and LS4FUTURE (LA/P/ 0087/2020) to CSM). AM was supported by a doctoral fellowship from FCT (PD/BD/128445/2017). ASR and MK were partially supported by grant UID/BIM/0009/2020 for the Research Center for Toxicogenomics and Human Health - (ToxOmics) from FCT, Portugal.
PY - 2022/7/15
Y1 - 2022/7/15
N2 - Adequate alternatives to conventional animal testing are needed to study developmental neurotoxicity (DNT). Here, we used kinematic analysis to assess DNT of known (toluene (TOL) and chlorpyrifos (CPS)) and putative (β-N-methylamino-L-alanine (BMAA)) neurotoxic compounds.
Drosophila melanogaster was exposed to these compounds during development and evaluated for survival and adult kinematic parameters using the FlyWalker system, a kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Moreover, while TOL did not significantly induce lethality or kinematic dysfunction, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO. Interestingly, BMAA, which was not lethal during development, induced motor decay in young adult animals, phenotypically resembling aged flies, an effect later attenuated upon aging. Furthermore, BMAA induced abnormal development of leg motor neuron projections. Our results suggest that our kinematic approach can assess potential DNT of chemical compounds.
AB - Adequate alternatives to conventional animal testing are needed to study developmental neurotoxicity (DNT). Here, we used kinematic analysis to assess DNT of known (toluene (TOL) and chlorpyrifos (CPS)) and putative (β-N-methylamino-L-alanine (BMAA)) neurotoxic compounds.
Drosophila melanogaster was exposed to these compounds during development and evaluated for survival and adult kinematic parameters using the FlyWalker system, a kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Moreover, while TOL did not significantly induce lethality or kinematic dysfunction, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO. Interestingly, BMAA, which was not lethal during development, induced motor decay in young adult animals, phenotypically resembling aged flies, an effect later attenuated upon aging. Furthermore, BMAA induced abnormal development of leg motor neuron projections. Our results suggest that our kinematic approach can assess potential DNT of chemical compounds.
KW - Entomology
KW - Neurotoxicology
U2 - 10.1016/j.isci.2022.104541
DO - 10.1016/j.isci.2022.104541
M3 - Article
C2 - 35769875
SN - 2589-0042
VL - 25
JO - ISCIENCE
JF - ISCIENCE
IS - 7
M1 - 104541
ER -