Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease

Parkinson's disease (PD) is among the most prevalent neurodegenerative disorders and is diagnosed based on motor symptoms that emerge after significant dopaminergic neuron loss. Non-motor symptoms, such as constipation, are the most common and often appear earlier, indicating the onset of the d...

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Autores: Muñoz-Juan, Amanda, Laromaine, Anna, Yuste, Víctor J, Dalfó, Esther
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
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dc.title.none.fl_str_mv Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
title Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
spellingShingle Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
Muñoz-Juan, Amanda
title_short Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
title_full Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
title_fullStr Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
title_full_unstemmed Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
title_sort Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's Disease
dc.creator.none.fl_str_mv Muñoz-Juan, Amanda
Laromaine, Anna
Yuste, Víctor J
Dalfó, Esther
author Muñoz-Juan, Amanda
author_facet Muñoz-Juan, Amanda
Laromaine, Anna
Yuste, Víctor J
Dalfó, Esther
author_role author
author2 Laromaine, Anna
Yuste, Víctor J
Dalfó, Esther
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Generalitat de Catalunya
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Parkinson's disease (PD) is among the most prevalent neurodegenerative disorders and is diagnosed based on motor symptoms that emerge after significant dopaminergic neuron loss. Non-motor symptoms, such as constipation, are the most common and often appear earlier, indicating the onset of the disease. Many animal models are used to study neurodegenerative diseases, yet most focus on the later stages. Because it is difficult to determine the exact start of neurodegeneration, no single model fully represents the entire disease progression. Mammalian models are especially time-consuming and expensive due to their long-life cycles. In contrast, Caenorhabditis elegans (C. elegans), a transparent 1 mm nematode with a short life and reproductive cycle (~3 weeks and 3 days), enables faster, cost-effective experiments thanks to its rapid generation turnover. The defecation motor program in C. elegans consists of rhythmic cycles regulated by a complex genetic network in which Rho/rac GTPases participate, and RAC1 (CED-10 in C. elegans) is among them. We have shown that RAC1/CED-10 mutants exhibit compromised GABAergic morphology and function, which results in disrupted defecation cycles. Here, we present the experimental protocol for measuring constipation in RAC1/CED-10 C. elegans at early stages. In addition to serving as a predictive tool to investigate early PD symptoms prior to neurodegeneration, this protocol could also be employed as an early endpoint to assess the efficacy of pharmacological intervention. Because these changes are not disease-specific, we believe this model provides a valuable tool for investigating alterations that arise early in other illnesses.
publishDate 2025
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2026
2026
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Journal of visualized experiments : JoVE
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dc.publisher.none.fl_str_mv Journal of Visualized Experiments
publisher.none.fl_str_mv Journal of Visualized Experiments
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spelling Assessing Gastrointestinal Motility in Caenorhabditis elegans RAC1/CED-10 Mutants as a Tool to Study Early Parkinson's DiseaseMuñoz-Juan, AmandaLaromaine, AnnaYuste, Víctor JDalfó, EstherParkinson's disease (PD) is among the most prevalent neurodegenerative disorders and is diagnosed based on motor symptoms that emerge after significant dopaminergic neuron loss. Non-motor symptoms, such as constipation, are the most common and often appear earlier, indicating the onset of the disease. Many animal models are used to study neurodegenerative diseases, yet most focus on the later stages. Because it is difficult to determine the exact start of neurodegeneration, no single model fully represents the entire disease progression. Mammalian models are especially time-consuming and expensive due to their long-life cycles. In contrast, Caenorhabditis elegans (C. elegans), a transparent 1 mm nematode with a short life and reproductive cycle (~3 weeks and 3 days), enables faster, cost-effective experiments thanks to its rapid generation turnover. The defecation motor program in C. elegans consists of rhythmic cycles regulated by a complex genetic network in which Rho/rac GTPases participate, and RAC1 (CED-10 in C. elegans) is among them. We have shown that RAC1/CED-10 mutants exhibit compromised GABAergic morphology and function, which results in disrupted defecation cycles. Here, we present the experimental protocol for measuring constipation in RAC1/CED-10 C. elegans at early stages. In addition to serving as a predictive tool to investigate early PD symptoms prior to neurodegeneration, this protocol could also be employed as an early endpoint to assess the efficacy of pharmacological intervention. Because these changes are not disease-specific, we believe this model provides a valuable tool for investigating alterations that arise early in other illnesses.A.M.J. acknowledges the Ph.D. scholarship (FPU18/05190) in the framework of the Biotechnology Ph.D. at Universitat Autònoma de Barcelona. AL and AMJ acknowledge the funding PID2021-122645OB-100 and PID2024-1576370B-100 by MCIN/AEI//10.13039/501100011033/FEDER "Una manera de hacer Europa"; the "Severo Ochoa" Programme for Centres of Excellence, in R&D CEX2019-000917-S (FUNFUTURE), CEX2023-001263-S (MATRANS42), Generalitat de Catalunya 2021S00446, and European Union's Horizon Europe research and innovation program under grant agreement No 101057527 (NextGEM). EDC acknowledges support from the APR-2024 grant (PMI24006), funded by the Fundació d'Estudis Superiors en Ciències de la Salut (FESS) and the Fundació Institut de Recerca i Innovació en Ciències de la Vida i la Salut de Catalunya (IRIS-CC).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S). With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2023-001263-S).Peer reviewedJournal of Visualized ExperimentsMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Generalitat de CatalunyaEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/430331https://api.elsevier.com/content/abstract/scopus_id/105024997835reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN/Plan Estatal de investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122645OB-100info:eu-repo/grantAgreement/MICINN/Plan Estatal de investigación Científica y Técnica y de Innovación 2024-2027/PID2024-1576370B-100info:eu-repo/grantAgreement/AEI/Plan Estatal de investigación Científica y Técnica y de Innovación 2017-2020/CEX2019-000917-Sinfo:eu-repo/grantAgreement/AEI/Plan Estatal de investigación Científica y Técnica y de Innovación 2021-2023/CEX2023-001263-Sinfo:eu-repo/grantAgreement/EC/HE/101057527Journal of visualized experiments : JoVEhttp://doi.org/10.3791/69278Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::12502adf118df1be8f10a5142a7115812026-05-22T06:33:51Z
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