The Nematode, Caenorhabditis elegans, as an Emerging Model for Investigating Epilepsy

Locke, Cody J.; Caldwell, Kim A.

doi:10.1007/978-1-60327-263-6_1

Cited by 4 publications

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“…These studies underscore the utility of both mammalian and non-mammalian models to reveal cellular effectors of neuronal activity (Locke et al 2009). Accordingly, several reports from a variety of animal models further implicate members of a Racsignaling pathway in seizures and epilepsy.…”

Section: Resultsmentioning

confidence: 97%

“…PILEPSY affects 1-2% of the world population and is associated with imbalances between excitatory and inhibitory neurotransmission in the brain (Locke et al 2009). In particular, interneurons expressing gammaaminobutyric acid (GABA), the principal inhibitory neurotransmitter in the human brain, are essential for normal neuronal synchronization and maintenance of a seizure threshold in humans (Cossette et al 2002), rodents (Delorey et al 1998), and zebrafish (Baraban et al 2005).…”

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confidence: 99%

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Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases inCaenorhabditis elegansGABAergic Neurotransmission

et al. 2009

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The nerve-cell cytoskeleton is essential for the regulation of intrinsic neuronal activity. For example, neuronal migration defects are associated with microtubule regulators, such as LIS1 and dynein, as well as with actin regulators, including Rac GTPases and integrins, and have been thought to underlie epileptic seizures in patients with cortical malformations. However, it is plausible that post-developmental functions of specific cytoskeletal regulators contribute to the more transient nature of aberrant neuronal activity and could be masked by developmental anomalies. Accordingly, our previous results have illuminated functional roles, distinct from developmental contributions, for Caenorhabditis elegans orthologs of LIS1 and dynein in GABAergic synaptic vesicle transport. Here, we report that C. elegans with function-altering mutations in canonical Rac GTPase-signaling-pathway members demonstrated a robust behavioral response to a GABA A receptor antagonist, pentylenetetrazole. Rac mutants also exhibited hypersensitivity to an acetylcholinesterase inhibitor, aldicarb, uncovering deficiencies in inhibitory neurotransmission. RNA interference targeting Rac hypomorphs revealed synergistic interactions between the dynein motor complex and some, but not all, members of Rac-signaling pathways. These genetic interactions are consistent with putative Rac-dependent regulation of actin and microtubule networks and suggest that some cytoskeletal regulators cooperate to uniquely govern neuronal synchrony through dynein-mediated GABAergic vesicle transport in C. elegans.

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Section: Resultsmentioning

confidence: 97%

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confidence: 99%

Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases inCaenorhabditis elegansGABAergic Neurotransmission

et al. 2009

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“…In contrast, although the nematode Caenorhabditis elegans has been extensively used to model a wide variety of neurological disorders ( Chen et al, 2015a ), there are relatively few studies where it has been used as a model organism for the study of epilepsy ( Jospin et al, 2009 ; Pandey et al, 2010 ; Risley et al, 2016 ; Williams et al, 2004 ). However, early observations of PTZ-inducible seizure-like phenotypes ( Locke et al, 2009 ; Williams et al, 2004 ) suggest the possibility of developing C. elegans platforms to replace conventional PTZ-induced rodent seizure models for early-stage AED discovery. This presents an attractive alternative, as the use of C. elegans offers various important advantages.…”

Section: Introductionmentioning

confidence: 99%

A Caenorhabditis elegans assay of seizure-like activity optimised for identifying antiepileptic drugs and their mechanisms of action

Wong

Jones

Dodd

et al. 2018

Journal of Neuroscience Methods

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“…Locke et al 2009, Dimitriade & Hart 2010Ewald & Li 2010, Harrington et al 2010, Piernaar et al 2010, Harrington et al 2011Kao et al 2011, Van Ham & Nollen 2011Zhou et al 2011).…”

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confidence: 99%

1. Morphology of Nematoda

Decraemer¹,

Coomans²,

Baldwin³

2013

Nematoda

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The Nematode, Caenorhabditis elegans, as an Emerging Model for Investigating Epilepsy

Cited by 4 publications

References 66 publications

Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases inCaenorhabditis elegansGABAergic Neurotransmission

Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases inCaenorhabditis elegansGABAergic Neurotransmission

A Caenorhabditis elegans assay of seizure-like activity optimised for identifying antiepileptic drugs and their mechanisms of action

1. Morphology of Nematoda

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