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

Abstract

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 Pb 2+ for 1 h. Thereafter, dopaminergic (DAergic) neurodegeneration, behavior and gene expression levels were assessed. The results revealed that Pb 2+ 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, Pb 2+ 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 Pb 2+ when compared with controls. In summary, our results revealed that Pb 2+ exposure induced dopaminergic dysfunction in C. elegans by altering dat-1 gene levels, but pkc mutants showed significant resistance to Pb 2+ toxicity. We conclude that PKC activation is directly involved in the neurotoxicity of Pb.

Modeling neurodegeneration in Caenorhabditis elegans

“…The BSR assay can elucidate pathways leading to the dysfunction and death of dopaminergic neurons when exposed to toxic substances. As examples, lead (Pb 2+ ) exposure increases dopaminergic neurotoxicity in wild-type C. elegans , but protein kinase ( pkc ) mutant animals are resistant, an effect that can be quantified via the BSR assay ( Akinyemi et al, 2019 ). Similarly, BSR assays have revealed that Akt signaling provides resistance to manganese-induced dopaminergic neurotoxicity ( Peres et al, 2019 ).…”

Effects of the occupational exposure on health status among petroleum station workers, Khartoum State, Sudan

“…Another recent study by Akinyemi et al [ 41 ] investigated the impact of lead exposure on dopaminergic neurodegeneration and functioning, which revealed that the activation of protein kinase C is directly associated with neurotoxicity of lead. The study by Akinyemi et al [ 41 ] was further extended by Renieri et al [ 42 ], who investigated the presence of cadmium, lead, and mercury in muscle tissue of seabass and gilthead seabream. The results demonstrated that the species of seabass and gilthead seabream were safe for all the tested metals.…”

The Effect of Lead Exposure on Autism Development

“…The accumulation of lead in the body has various consequences on the functioning of the central nervous system (CNS) [ 7 , 9 , 11 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Previous studies have highlighted alterations in several neurological mechanisms subsequent to lead exposure [ 7 , 9 , 11 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Prior research has emphasized the role of proper molecular structure in the adequate functioning of neurological mechanisms [ 36 ].…”

“…Metals have been shown to induce these transformations and dysfunctionalities within neurological systems [ 30 ]. Lead, in particular has been associated with the alteration of the release and reuptake of several neurotransmitters [ 30 ].…”