Nickel-Induced Developmental Neurotoxicity in C. elegans Includes Cholinergic, Dopaminergic and GABAergic Degeneration, Altered Behaviour, and Increased SKN-1 Activity.
Neurotox Res
; 37(4): 1018-1028, 2020 Apr.
Article
em En
| MEDLINE
| ID: mdl-32034695
ABSTRACT
Nickel (Ni) is a ubiquitous metal in the environment with increasing industrial application. While environmental and occupational exposure to Ni compounds has been known to result in toxicities to several organs, including the liver, kidney, lungs, skin and gonads, neurotoxic effects have not been extensively investigated. In this present study, we investigated specific neuronal susceptibility in a C. elegans model of acute Ni neurotoxicity. Wild-type worms and worms expressing green fluorescent protein (GFP) in either cholinergic, dopaminergic or GABAergic neurons were treated with NiCl2 for 1 h at the first larval (L1) stage. The median lethal dose (LD50) was calculated to be 5.88 mM in this paradigm. Morphology studies of GFP-expressing worms showed significantly increasing degeneration of cholinergic, dopaminergic and GABAergic neurons with increasing Ni concentration. Significant functional changes in locomotion and basal slowing response assays reflected that cholinergic and dopaminergic neuronal function, respectively, were impaired due to Ni treatment. Interestingly, a small but significant number of worms exhibited shrinker phenotype upon Ni exposure but no loopy head foraging behaviour was observed suggesting that function of D-type GABAergic neurons of C elegans may be specifically attenuated while the RME subset of GABAergic neurons are not. GFP expression due to induction of glutathione S-transferase 4 (gst-4), a target of Nrf2 homolog skn-1, was increased in a Pgst-4GFP worm highlighting Ni-induced oxidative stress. RT-qPCR verified upregulation of this expression of gst-4 immediately after exposure. These data suggest that oxidative stress is associated with neuronal damage and altered behaviour due to developmental Ni exposure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas de Caenorhabditis elegans
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Proteínas de Ligação a DNA
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Neurônios Colinérgicos
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Neurônios Dopaminérgicos
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Neurônios GABAérgicos
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Degeneração Neural
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Níquel
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurotox Res
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos