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Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson’s disease, Alzheimer’s disease and autism spectrum disorder

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Invertebrate Neuroscience

Abstract

The nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways that might be underpin complex human neurological diseases. Here, the role C. elegans is playing in understanding two neurodegenerative conditions, Parkinson’s and Alzheimer’s disease (AD), and a complex neurological condition, autism, is used as an exemplar of the utility of this model system. C. elegans is an imperfect model of Parkinson’s disease because it lacks orthologues of the human disease-related genes PARK1 and LRRK2 which are linked to the autosomal dominant form of this disease. Despite this fact, the nematode is a good model because it allows transgenic expression of these human genes and the study of the impact on dopaminergic neurons in several genetic backgrounds and environmental conditions. For AD, C. elegans has orthologues of the amyloid precursor protein and both human presenilins, PS1 and PS2. In addition, many of the neurotoxic properties linked with Aβ amyloid and tau peptides can be studied in the nematode. Autism spectrum disorder is a complex neurodevelopmental disorder characterised by impairments in human social interaction, difficulties in communication, and restrictive and repetitive behaviours. Establishing C. elegans as a model for this complex behavioural disorder is difficult; however, abnormalities in neuronal synaptic communication are implicated in the aetiology of the disorder. Numerous studies have associated autism with mutations in several genes involved in excitatory and inhibitory synapses in the mammalian brain, including neuroligin, neurexin and shank, for which there are C. elegans orthologues. Thus, several molecular pathways and behavioural phenotypes in C. elegans have been related to autism. In general, the nematode offers a series of advantages that combined with knowledge from other animal models and human research, provides a powerful complementary experimental approach for understanding the molecular mechanisms and underlying aetiology of complex neurological diseases.

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Acknowledgments

We thank Prof. Lindy M. Holden-Dye for critical reading of the manuscript and for detailed comments. We also are grateful to Dr. Antonio Miranda-Vizuete for his help with the DiI dye-filling assay and valuable support. This work was supported by grant PI0197, Consejería de Salud, Junta de Andalucía.

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  1. Departamento de Genética, Edificio Gregor Mendel, Universidad de Córdoba, Campus de Rabanales, 14071, Córdoba, Spain

    Fernando Calahorro & Manuel Ruiz-Rubio

  2. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14071, Córdoba, Spain

    Fernando Calahorro & Manuel Ruiz-Rubio

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  1. Fernando Calahorro
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  2. Manuel Ruiz-Rubio
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Correspondence to Manuel Ruiz-Rubio.

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Calahorro, F., Ruiz-Rubio, M. Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson’s disease, Alzheimer’s disease and autism spectrum disorder. Invert Neurosci 11, 73–83 (2011). https://doi.org/10.1007/s10158-011-0126-1

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  • DOI: https://doi.org/10.1007/s10158-011-0126-1

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