Strengths and limitations of morphological and behavioral analyses in detecting dopaminergic deficiency in Caenorhabditis elegans

Smith, Latasha L.; Ryde, Ian T.; Hartman, Jessica H.; Romersi, Riccardo F.; Markovich, Zachary; Meyer, Joel N.

doi:10.1016/j.neuro.2019.07.002

Cited by 18 publications

(13 citation statements)

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“…C. elegans have been widely used as a model for ageing [ 32 ], with their short lifespan and rapid reproduction rate facilitating straightforward and fast study of this process. C.elegans are highly amenable to neurobiology, as they have a fully mapped neural connectome [ 33 , 34 ], in which each neuron is characterised in its neurochemistry, connectivity and functionality, often with attributable behavioural phenotypes to each neural circuit to test [ 35 , 36 ]. Furthermore, the majority of neurotransmitters utilised in neuronal signalling in the human brain, are also produced and utilised in the C. elegans neuronal system [ 30 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

“…C. elegans present a range of PD relevant behavioural and organismal phenotypes to characterise and test, as outputs of gene function, which range from specific dopaminergic neuron attributable behaviours [ 36 , 48–50 ], in vivo microscopy [ 51 ], to organismal responses to environmental stressors [ 35 ], as summarised in Figure 2 . Comprehensive and recent reviews of PD relevant phenotypes in C. elegans can be found elsewhere [ 21 , 35 ], and open access databases such as WormBase and WormBook contain extensive, up-to-date information on organism genes, C. elegans biology and experimental protocols [ 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, C. elegans are highly amenable to environmental toxin assays and drug screens to evaluate the interplay with transgenic expression of human proteins of interest [ 153 , 154 ]. C. elegans strains overexpressing the PD associated LRRK2 G2019S and LRRK2 R1441C mutant proteins in neurons show reduced survival in response to oxidative stress induced by the environmental toxins rotenone and paraquat, widely used in toxin-based models of PD [ 155 ], when compared with animals expressing wild-type LRRK2 [ 142 , 148 ].…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Multiple genetic approaches can be utilised to investigate gene function in C. elegans. PD pathology can be investigated in C. elegans through in vivo microscopy (51), using established cellular reporters of dopaminergic neuron degeneration, α-synuclein aggregation, mitochondria network and lysosomal function (35,36). In this review, we will evaluate the potential modelling approaches of the functional genetics of PD using C. elegans.…”

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confidence: 99%

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Modelling the functional genomics of Parkinson’s disease inCaenorhabditis elegans:LRRK2and beyond

et al. 2021

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For decades, Parkinson’s disease (PD) cases have been genetically categorised into familial, when caused by mutations in single genes with a clear inheritance pattern in affected families, or idiopathic, in the absence of an evident monogenic determinant. Recently, genome-wide association studies (GWAS) have revealed how common genetic variability can explain up to 36% of PD heritability and that PD manifestation is often determined by multiple variants at different genetic loci. Thus, one of the current challenges in PD research stands in modelling the complex genetic architecture of this condition and translating this into functional studies. Caenorhabditis elegans provide a profound advantage as a reductionist, economical model for PD research, with a short lifecycle, straightforward genome engineering and high conservation of PD relevant neural, cellular and molecular pathways. Functional models of PD genes utilising C. elegans, show many phenotypes recapitulating pathologies observed in PD. When contrasted with mammalian in vivo and in vitro models, these are frequently validated, suggesting relevance of C. elegans in the development of novel PD functional models. This review will discuss how the nematode C. elegans PD models have contributed to the uncovering of molecular and cellular mechanisms of disease, with a focus on the genes most commonly found as causative in familial PD and risk factors in idiopathic PD. Specifically, we will examine the current knowledge on a central player in both familial and idiopathic PD, Leucine-rich repeat kinase 2 (LRRK2) and how it connects to multiple PD associated GWAS candidates and Mendelian disease-causing genes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Modelling the functional genomics of Parkinson’s disease inCaenorhabditis elegans:LRRK2and beyond

et al. 2021

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Hordenine improves Parkinsonian‐like motor deficits in mice and nematodes by activating dopamine D2 receptor‐mediated signaling

Liu

Gao

Chen

et al. 2023

Phytotherapy Research

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Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum, leading to dopamine (DA) deficiency in the striatum and typical motor symptoms. A small molecule as a dietary supplement for PD would be ideal for practical reasons. Hordenine (HOR) is a phenolic phytochemical marketed as a dietary supplement found in cereals and germinated barley, as well as in beer, a widely consumed beverage. This study was aimed to identify HOR as a dopamine D2 receptor (DRD2) agonist in living cells, and investigate the alleviative effect and mechanism of HOR on PD-like motor deficits in mice and nematodes. Our results firstly showed that HOR is an agonist of DRD2, but not DRD1, in living cells. Moreover, HOR could improve the locomotor dysfunction, gait, and postural imbalance in MPTP-or 6-OHDA-induced mice or Caenorhabditis elegans, and prevent α-synuclein accumulation via the DRD2 pathway in C. elegans. Our results suggested that HOR could activate DRD2 to attenuate the PD-like motor deficits, and provide scientific evidence for the safety and reliability of HOR as a dietary supplement.

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Caenorhabditis elegans: an elegant model organism for evaluating the neuroprotective and neurotherapeutic potential of nutraceuticals

Darvesh¹,

Barnett²,

Fitsanakis³

2021

Nutraceuticals

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Strengths and limitations of morphological and behavioral analyses in detecting dopaminergic deficiency in Caenorhabditis elegans

Cited by 18 publications

References 51 publications

Modelling the functional genomics of Parkinson’s disease inCaenorhabditis elegans:LRRK2and beyond

Modelling the functional genomics of Parkinson’s disease inCaenorhabditis elegans:LRRK2and beyond

Hordenine improves Parkinsonian‐like motor deficits in mice and nematodes by activating dopamine D2 receptor‐mediated signaling

Caenorhabditis elegans: an elegant model organism for evaluating the neuroprotective and neurotherapeutic potential of nutraceuticals

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