XB-ART-47372
Dis Model Mech
2013 Sep 01;65:1057-65. doi: 10.1242/dmm.012138.
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Modeling human neurodevelopmental disorders in the Xenopus tadpole: from mechanisms to therapeutic targets.
Pratt KG
,
Khakhalin AS
.
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The Xenopus tadpole model offers many advantages for studying the molecular, cellular and network mechanisms underlying neurodevelopmental disorders. Essentially every stage of normal neural circuit development, from axon outgrowth and guidance to activity-dependent homeostasis and refinement, has been studied in the frog tadpole, making it an ideal model to determine what happens when any of these stages are compromised. Recently, the tadpole model has been used to explore the mechanisms of epilepsy and autism, and there is mounting evidence to suggest that diseases of the nervous system involve deficits in the most fundamental aspects of nervous system function and development. In this Review, we provide an update on how tadpole models are being used to study three distinct types of neurodevelopmental disorders: diseases caused by exposure to environmental toxicants, epilepsy and seizure disorders, and autism.
???displayArticle.pubmedLink??? 23929939
???displayArticle.pmcLink??? PMC3759326
???displayArticle.link??? Dis Model Mech
???displayArticle.grants??? [+]
P30 GM103398 NIGMS NIH HHS , R01 EY019578-03 NEI NIH HHS , P30 RR032128 NCRR NIH HHS , R01 EY019578 NEI NIH HHS
Species referenced: Xenopus
Genes referenced: tbx2
GO keywords: nervous system development
???displayArticle.disOnts??? autism spectrum disorder
???displayArticle.omims??? AUTISM
???attribute.lit??? ???displayArticles.show???
Fig. 1. The Xenopus tadpole as a research model, shown with key experimental techniques that are used to differentiate between normal and abnormal patterns of neural development. (1) Top: view of the animal at ca. 3 weeks post-fertilization. Several behavioral tests can be used to assess brain development: for example, wild-type animals usually swim along the sides of the container (represented by a circle; bottom), whereas animals with altered excitation/inhibition balance tend to circle in the middle of it. (2) Top: general view of the brain. OB, olfactory bulbs; OT, optic tectum; HB, hindbrain: SC, spinal cord; red, projections from the retina; green, tectal projections to the hindbrain; blue, descending projections to the spinal cord. An isolated brain provides an accessible in vitro preparation, and whole-brain immunostaining (bottom) can be used to quantify global alterations in brain biochemistry (an exaggerated staining for GABA is shown). (3) Top: horizontal section of the optic tectum (OT) and caudal forebrain (FB); at this level, Ca2+ imaging can be used to detect abnormal seizure-like patterns of activity (bottom). (4) At the neuron level, in vivo or ex vivo imaging allows assessment of cell morphology development. (5) At the synaptic level, electrophysiology offers a way to quantify maturation of synaptic and intrinsic properties of the cell through recordings of (a) evoked synaptic responses, (b) spiking in response to current injections and (c) spontaneous synaptic activity. The figure is inspired by experimental data published in the following papers: (Aizenman et al., 2002; Bestman et al., 2006; Ruthazer et al., 2006; Pratt and Aizenman, 2007; Hewapathirane et al., 2008; Bollmann and Engert, 2009; Hiramoto and Cline, 2009; Straka, 2010; Bell et al., 2011; Marshak et al., 2012; Miraucourt et al., 2012). |
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