Morphological hallmarks of dopaminergic neurodegeneration are associated with altered neuron function in Caenorhabditis elegans.
Neurotoxicology
; 100: 100-106, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38070655
ABSTRACT
Caenorhabditis elegans (C. elegans) is an excellent model system to study neurodegenerative diseases, such as Parkinson's disease, as it enables analysis of both neuron morphology and function in live animals. Multiple structural changes in neurons, such as cephalic dendrite morphological abnormalities, have been considered hallmarks of neurodegeneration in this model, but their relevance to changes in neuron function are not entirely clear. We sought to test whether hallmark morphological changes associated with chemically induced dopaminergic neuron degeneration, such as dendrite blebbing, breakage, and loss, are indicative of neuronal malfunction and result in changes in behavior. We adapted an established dopaminergic neuronal function assay by measuring paralysis in the presence of exogenous dopamine, which revealed clear differences between cat-2 dopamine deficient mutants, wildtype worms, and dat-1 dopamine abundant mutants. Next, we integrated an automated image processing algorithm and a microfluidic device to segregate worm populations by their cephalic dendrite morphologies. We show that nematodes with dopaminergic dendrite degeneration markers, such as blebbing or breakage, paralyze at higher rates in a dopamine solution, providing evidence that dopaminergic neurodegeneration morphologies are correlated with functional neuronal outputs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article