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dc.contributor.author
Eagleson, K. L.
dc.contributor.author
Gravielle, Maria Clara
dc.contributor.author
Schlueter McFadyen Ketchum, L. J.
dc.contributor.author
Russek, S. J.
dc.contributor.author
Farb, D. H.
dc.contributor.author
Levitt, P.
dc.date.available
2019-01-07T19:53:58Z
dc.date.issued
2010-07
dc.identifier.citation
Eagleson, K. L.; Gravielle, Maria Clara; Schlueter McFadyen Ketchum, L. J.; Russek, S. J.; Farb, D. H.; et al.; Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes; Pergamon-Elsevier Science Ltd; Neuroscience; 168; 3; 7-2010; 797-810
dc.identifier.issn
0306-4522
dc.identifier.uri
http://hdl.handle.net/11336/67618
dc.description.abstract
Disruption of the GABAergic system has been implicated in multiple developmental disorders, including epilepsy, autism spectrum disorder and schizophrenia. The human gene encoding uPAR (PLAUR) has been shown recently to be associated with the risk of autism. The uPAR-/- mouse exhibits a regionally-selective reduction in GABAergic interneurons in frontal and parietal regions of the cerebral cortex as well as in the CA1 and dentate gyrus subfields of the hippocampus. Behaviorally, these mice exhibit increased sensitivity to pharmacologically-induced seizures, heightened anxiety, and atypical social behavior. Here, we explore potential alterations in GABAergic circuitry that may occur in the context of altered interneuron development. Analysis of gene expression for 13 GABAA receptor subunits using quantitative real-time polymerase chain reaction (PCR) indicates seven subunit mRNAs (α1, α2, α3, β2, β3, γ2S and γ2L) of interest. Semi-quantitative in situ hybridization analysis focusing on these subunit mRNAs reveals a complex pattern of potential gene regulatory adaptations. The levels of α2 subunit mRNAs increase in frontal cortex, CA1 and CA3, while those of α3 decrease in frontal cortex and CA1. In contrast, α1 subunit mRNAs are unaltered in any region examined. β2 subunit mRNAs are increased in frontal cortex whereas β3 subunit mRNAs are decreased in parietal cortex. Finally, γ2S subunit mRNAs are increased in parietal cortex while γ2L subunit mRNAs are increased in the dentate gyrus, potentially altering the γ2S:γ2L ratio in these two regions. For all subunits, no changes were observed in forebrain regions where GABAergic interneuron numbers are normal. We propose that disrupted differentiation of GABAergic neurons specifically in frontal and parietal cortices leads to regionally-selective alterations in local circuitry and subsequent adaptive changes in receptor subunit composition. Future electrophysiological studies will be useful in determining how alterations in network activity in the cortex and hippocampus relate to the observed behavioral phenotype.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Hippocampus
dc.subject
Interneurons
dc.subject
Neocortex
dc.subject
Neurodevelopmental Disorders
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-07T13:32:27Z
dc.journal.volume
168
dc.journal.number
3
dc.journal.pagination
797-810
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Eagleson, K. L.. University of Southern California; Estados Unidos
dc.description.fil
Fil: Gravielle, Maria Clara. Boston University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Schlueter McFadyen Ketchum, L. J.. University of Southern California; Estados Unidos
dc.description.fil
Fil: Russek, S. J.. Boston University; Estados Unidos
dc.description.fil
Fil: Farb, D. H.. Boston University; Estados Unidos
dc.description.fil
Fil: Levitt, P.. University of Southern California; Estados Unidos
dc.journal.title
Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neuroscience.2010.03.066
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0306452210005014


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