Lead (Pb) exposure induces dopaminergic neurotoxicity in Caenorhabditis elegans: Involvement of the dopamine transporter

Lead (Pb) is an environmental neurotoxicant, and has been implicated in several neurological disorders of dopaminergic dysfunction; however, the molecular mechanism of its toxicity has yet to be fully understood. This study investigated the effect of Pb exposure on dopaminergic neurodegeneration and function, as well as expression level of several dopaminergic signaling genes in wild type (N2) and protein kinase C (pkc) mutant Caenorhabditis elegans. Both N2 and pkc mutant worms were exposed to Pb2+ for 1 h. Thereafter, dopaminergic (DAergic) neurodegeneration, behavior and gene expression levels were assessed. The results revealed that Pb2+ treatment affects dopaminergic cell morphology and structure in worms expressing green fluorescent protein (GFP) under a DAergic cell specific promoter. Also, there was a significant impairment in dopaminergic neuronal function as tested by basal slowing response (BSR) in wild-type, N2 worms, but no effect was observed in pkc mutant worms. Furthermore, Pb2+ exposure increased dat-1 gene expression level when compared with N2 worms, but no alteration was observed in the pkc mutant strains. LC–MS analysis revealed a significant decrease in dopamine content in worms treated with Pb2+ when compared with controls. In summary, our results revealed that Pb2+ exposure induced dopaminergic dysfunction in C. elegans by altering dat-1 gene levels, but pkc mutants showed significant resistance to Pb2+ toxicity. We conclude that PKC activation is directly involved in the neurotoxicity of Pb. © 2019

Akinyemi A.J.1 , Miah M.R.1 , Ijomone O.M.1, 2 , Tsatsakis A.3 , Soares F.A.A.1, 4 , Tinkov A.A. 5 , Skalny A.V. 6, 7 , Venkataramani V.8, 9 , Aschner M.1
Elsevier Inc.
  • 1 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States
  • 2 Department of Anatomy, School of Health and Health Technology, Federal University of Technology Akure (FUTA), Nigeria
  • 3 Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, Heraklion, Greece
  • 4 Universidade Federal de Santa Maria, Centro de Ciências Naturais e Exatas, Departamento de Bioquímica e Biologia Molecular, Santa Maria, RS, Brazil
  • 5 Yaroslavl State University, Yaroslavl, Russian Federation
  • 6 Peoples’ Friendship, University of Russia (RUDN University), Moscow, Russian Federation
  • 7 I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  • 8 Department of Hematology and Medical Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany
  • 9 Institute of Pathology, University Medical Center Göttingen (UMG), Göttingen, Germany
Ключевые слова
dat-1; Dopaminergic neuron; Neurotoxicant; Pb; PKC
Дата создания
Дата изменения
Постоянная ссылка

Другие записи

Choroba K., Machura B., Kula S., Raposo L.R., Fernandes A.R., Kruszynski R., Erfurt K., Shul'Pina L.S., Kozlov Y.N., Shul'Pin G.B.
Dalton Transactions. Royal Society of Chemistry. Том 48. 2019. С. 12656-12673