Linked Life Data

12533622

Source:http://linkedlifedata.com/resource/pubmed/id/12533622

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-20
pubmed:abstractText
The generation of properly functioning circuits during brain development requires precise timing of cell migration and differentiation. Disruptions in the developmental plan may lead to neurological and psychiatric disorders. Neocortical circuits rely on inhibitory GABAergic interneurons, the majority of which migrate from subcortical sources. We have shown that the pleiotropic molecule hepatocyte growth factor/scatter factor (HGF/SF) mediates interneuron migration. Mice with a targeted mutation of the gene encoding urokinase plasminogen activator receptor (uPAR), a key component in HGF/SF activation and function, have decreased levels of HGF/SF and a 50% reduction in neocortical GABAergic interneurons at embryonic and perinatal ages. Disruption of interneuron development leads to early lethality in most models. Thus, the long-term consequences of such perturbations are unknown. Mice of the uPAR-/- strain survive until adulthood, and behavior testing demonstrates that they have an increased anxiety state. The uPAR-/- strain also exhibits spontaneous seizure activity and higher susceptibility to pharmacologically induced convulsions. The neocortex of the adult uPAR-/- mouse exhibits a dramatic region- and subtype-specific decrease in GABA-immunoreactive interneurons. Anterior cingulate and parietal cortical areas contain 50% fewer GABAergic interneurons compared with wild-type littermates. However, interneuron numbers in piriform and visual cortical areas do not differ from those of normal mice. Characterization of interneuron subpopulations reveals a near complete loss of the parvalbumin subtype, with other subclasses remaining intact. These data demonstrate that a single gene mutation can selectively alter the development of cortical interneurons in a region- and cell subtype-specific manner, with deficits leading to long-lasting changes in circuit organization and behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
622-31
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12533622-Animals, pubmed-meshheading:12533622-Anxiety, pubmed-meshheading:12533622-Behavior, Animal, pubmed-meshheading:12533622-Calcium-Binding Proteins, pubmed-meshheading:12533622-Cell Count, pubmed-meshheading:12533622-Darkness, pubmed-meshheading:12533622-Electroencephalography, pubmed-meshheading:12533622-Epilepsy, pubmed-meshheading:12533622-Exploratory Behavior, pubmed-meshheading:12533622-GABA Antagonists, pubmed-meshheading:12533622-Genetic Predisposition to Disease, pubmed-meshheading:12533622-Interneurons, pubmed-meshheading:12533622-Light, pubmed-meshheading:12533622-Male, pubmed-meshheading:12533622-Mice, pubmed-meshheading:12533622-Mice, Inbred C57BL, pubmed-meshheading:12533622-Mice, Knockout, pubmed-meshheading:12533622-Neocortex, pubmed-meshheading:12533622-Receptors, Cell Surface, pubmed-meshheading:12533622-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:12533622-Spatial Behavior, pubmed-meshheading:12533622-gamma-Aminobutyric Acid
pubmed:year
2003
pubmed:articleTitle
Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction.
pubmed:affiliation
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. epowell@pitt.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.