Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.

Nature medicine | Oct 8, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19701204

A subset of central glutamatergic synapses are coordinately pruned and matured by unresolved mechanisms during postnatal development. We report that the human epilepsy gene LGI1, encoding leucine-rich, glioma-inactivated protein-1 and mutated in autosomal dominant lateral temporal lobe epilepsy (ADLTE), mediates this process in hippocampus. We created transgenic mice either expressing a truncated mutant LGI1 (835delC) found in ADLTE or overexpressing a wild-type LGI1. We discovered that the normal postnatal maturation of presynaptic and postsynaptic functions was arrested by the 835delC mutant LGI1, and contrastingly, was magnified by excess wild-type LGI1. Concurrently, mutant LGI1 inhibited dendritic pruning and increased the spine density to markedly increase excitatory synaptic transmission. Inhibitory transmission, by contrast, was unaffected. Furthermore, mutant LGI1 promoted epileptiform discharge in vitro and kindling epileptogenesis in vivo with partial gamma-aminobutyric acid(A) (GABA(A)) receptor blockade. Thus, LGI1 represents a human gene mutated to promote epilepsy through impaired postnatal development of glutamatergic circuits.

Pubmed ID: 19701204 RIS Download

Mesh terms: Animals | Epilepsy, Temporal Lobe | Gene Expression Regulation, Developmental | Genes, Dominant | Humans | Mice | Mice, Transgenic | Mutation | Proteins | Receptors, GABA-B | Synapses | Transgenes

Research resources used in this publication

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: K02 NS054674
  • Agency: NINDS NIH HHS, Id: K02 NS054674-03
  • Agency: NINDS NIH HHS, Id: K02 NS054674-04
  • Agency: NINDS NIH HHS, Id: R01 NS057444
  • Agency: NINDS NIH HHS, Id: R01 NS057444
  • Agency: NINDS NIH HHS, Id: R01 NS057444-02
  • Agency: NINDS NIH HHS, Id: R03 NS052521
  • Agency: NINDS NIH HHS, Id: R03 NS052521-02

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.