TY - JOUR
T1 - Developmental lead exposure affects dopaminergic neuron morphology and modifies basal slowing response in Caenorhabditis elegans
T2 - Effects of ethanol
AU - Albrecht, Paula A.
AU - Fernandez-Hubeid, Lucia E.
AU - Deza-Ponzio, Romina
AU - Martins, Airton C.
AU - Aschner, Michael
AU - Virgolini, Miriam B.
N1 - Funding Information:
The authors wish to thank the technical assistance of Nicolas Jaime and Javier Reparaz for their help with the maintenance of C. elegans. PA was granted a CONICET fellowship to pursue her Ph. D, and with a Fulbright fellowship for a short stay in the US. Supported in part by Fondo para la Investigación Científica y Tecnológica ( FONCyT ) BID PICT 2017-2989 and Secretaría de Ciencia y Tecnología ( SeCyT-UNC ) from Argentina (MBV) and National Institute of Environmental Health Sciences ( NIEHS ) R01ES07331 and R01ES10563 (MA).
Funding Information:
The assessment of DAergic morphology was performed in the BY200 [dat-1p::GFP (vtIs1) V] strain which expresses GFP under a DAergic cell specific promoter. For the BSR experiment the strains used were: Bristol N2: (wild-type) worms; MT15620: cat-2(n4547)II, that is a null mutant for TH; UA57: baIs4[dat-1p::GFP + dat-1p::CAT-2] that presents TH overexpression; CB1111: cat-1(e1111)X, null mutant for the vesicular monoamine transporter (VMAT); MAB398: dat-1p::GFP (vtIs1)V + dat-1(ok157)III, in which the DAergic neurons are GFP-tagged with null mutation for DAT; LX734: dop-2(vs105)V; dop-1(vs100) dop-3(vs106)X, null mutant for DOP-1, DOP-2 and DOP-3 receptors; and RB1254: C52B11.3(ok1321) X, null mutant for the postsynaptic receptor DOP-4. All strains were obtained from the Caenorhabditis Genetics Center (CGC), University of Minnesota, NM, USA, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440), except BY200 [dat-1p::GFP (vtIs1) V] that was kindly provided by the Blakely laboratory, Vanderbilt University Medical Center.
Funding Information:
The authors wish to thank the technical assistance of Nicolas Jaime and Javier Reparaz for their help with the maintenance of C. elegans. PA was granted a CONICET fellowship to pursue her Ph. D, and with a Fulbright fellowship for a short stay in the US. Supported in part by Fondo para la Investigación Científica y Tecnológica (FONCyT) BID PICT 2017-2989 and Secretaría de Ciencia y Tecnología (SeCyT-UNC) from Argentina (MBV) and National Institute of Environmental Health Sciences (NIEHS) R01ES07331 and R01ES10563 (MA).
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/7
Y1 - 2022/7
N2 - Lead (Pb) and ethanol (EtOH) are neurotoxicants that affect the dopaminergic (DAergic) system. We first sought to assess the morphology of the DAergic neurons in the Caenorhabditis elegans BY200 strain. The results demonstrated dose-dependent damage in these neurons induced by developmental Pb exposure. Secondly, transgenic worms exposed to 24 μM Pb and administered with 200 mM EtOH were evaluated in the basal slowing response (BSR). Pb induced impairment in the BSR in the wild-type strain that did not improve in response to EtOH, an effect also observed in strains that lack the DOP-1, DOP-2, and DOP-3 receptors. The animals that overexpress tyrosine hydroxylase (TH), or lack the vesicular transport (VMAT) showed a Pb-induced impairment in the BSR that seemed to improve after EtOH. Interestingly, a dramatic impairment in the BSR was observed in the Pb group in strains lacking the DOP-4 receptor, resembling the response of the TH-deficient strain, an effect that in both cases showed a non-significant reversal by EtOH. These results suggest that the facilitatory effect of EtOH on the impaired BSR observed in Pb-exposed null mutant strains may be the result of a compensatory effect in the altered DAergic synapse present in these animals.
AB - Lead (Pb) and ethanol (EtOH) are neurotoxicants that affect the dopaminergic (DAergic) system. We first sought to assess the morphology of the DAergic neurons in the Caenorhabditis elegans BY200 strain. The results demonstrated dose-dependent damage in these neurons induced by developmental Pb exposure. Secondly, transgenic worms exposed to 24 μM Pb and administered with 200 mM EtOH were evaluated in the basal slowing response (BSR). Pb induced impairment in the BSR in the wild-type strain that did not improve in response to EtOH, an effect also observed in strains that lack the DOP-1, DOP-2, and DOP-3 receptors. The animals that overexpress tyrosine hydroxylase (TH), or lack the vesicular transport (VMAT) showed a Pb-induced impairment in the BSR that seemed to improve after EtOH. Interestingly, a dramatic impairment in the BSR was observed in the Pb group in strains lacking the DOP-4 receptor, resembling the response of the TH-deficient strain, an effect that in both cases showed a non-significant reversal by EtOH. These results suggest that the facilitatory effect of EtOH on the impaired BSR observed in Pb-exposed null mutant strains may be the result of a compensatory effect in the altered DAergic synapse present in these animals.
KW - Lead – Ethanol – Dopamine – Caenorhabditis elegans
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U2 - 10.1016/j.neuro.2022.06.005
DO - 10.1016/j.neuro.2022.06.005
M3 - Article
C2 - 35724878
AN - SCOPUS:85134434713
SN - 0161-813X
VL - 91
SP - 349
EP - 359
JO - Neurotoxicology
JF - Neurotoxicology
ER -