Linked Life Data

17446080

Source:http://linkedlifedata.com/resource/pubmed/id/17446080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-5-22
pubmed:abstractText
Altered expression and distribution of neurotransmitter receptors, including metabotropic glutamate receptors (mGluRs), constitute key aspects in epileptogenesis, impaired hippocampal excitability and neuronal degeneration. mGluR1 mediates predominantly excitatory effects, whereas mGluR4 acts as inhibitory presynaptic receptor. Increased hippocampal expression of mGluR1 and mGluR4 has been observed in human temporal lobe epilepsy (TLE). In this study, we address whether genetic mGluR1 upregulation and mGluR4 knock-down influence seizure susceptibility and/or vulnerability of hippocampal neurons by analyzing transgenic animals in the pilocarpine TLE model. Therefore, we generated transgenic mice expressing mGluR1-enhanced green fluorescent protein (EGFP) fusion protein under control of the human cytomegalovirus (CMV) immediate early promoter. Status epilepticus (SE) was induced in (a) mice overexpressing mGluR1-EGFP and (b) mice deficient for mGluR4 (mGluR4 KO) as well as littermate controls. In the acute epileptic stage after pilocarpine application, mGluR4 KO mice showed a significant increase of severe seizure activity, in contrast to mGluR1 transgenics. Analysis of both transgenic mouse lines in the chronic epileptic phase, using a telemetric EEG-/video-monitoring system, revealed a significant increase in seizure frequency only in mGluR1-EGFP mice. In contrast, enhanced neuronal cell loss was only present in the hippocampus of epileptic mGluR4 KO mice. Our results suggest a role for mGluR1 in promoting seizure susceptibility as well as for mGluR4 to counteract excitatory activity and seizure-associated vulnerability of hippocampal neurons. Therefore, our data strongly recommend both mGluRs as potential drug targets to interfere with the development of hippocampal damage and seizure activity in TLE.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0969-9961
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
623-33
pubmed:dateRevised
2010-6-18
pubmed:meshHeading
pubmed-meshheading:17446080-Animals, pubmed-meshheading:17446080-Convulsants, pubmed-meshheading:17446080-Disease Models, Animal, pubmed-meshheading:17446080-Down-Regulation, pubmed-meshheading:17446080-Epilepsy, pubmed-meshheading:17446080-Epilepsy, Temporal Lobe, pubmed-meshheading:17446080-Gene Expression Regulation, pubmed-meshheading:17446080-Genetic Predisposition to Disease, pubmed-meshheading:17446080-Glutamic Acid, pubmed-meshheading:17446080-Green Fluorescent Proteins, pubmed-meshheading:17446080-Hippocampus, pubmed-meshheading:17446080-Mice, pubmed-meshheading:17446080-Mice, Knockout, pubmed-meshheading:17446080-Mice, Transgenic, pubmed-meshheading:17446080-Nerve Degeneration, pubmed-meshheading:17446080-Neurons, pubmed-meshheading:17446080-Pilocarpine, pubmed-meshheading:17446080-Receptors, Metabotropic Glutamate, pubmed-meshheading:17446080-Recombinant Fusion Proteins, pubmed-meshheading:17446080-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Functional role of mGluR1 and mGluR4 in pilocarpine-induced temporal lobe epilepsy.
pubmed:affiliation
Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, D-53105 Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't