Document Detail


STEP regulation of seizure thresholds in the hippocampus.
MedLine Citation:
PMID:  21204826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate whether striatal enriched protein tyrosine phosphatase (STEP) influences ictogenesis.
METHODS: STEP knockout mice were compared to wild-type (WT) mice in pilocarpine-induced seizures. Hippocampal slices were also prepared from these two mouse populations, allowing the examination of ictal-like stimulation in these slices using calcium imaging and electrophysiologic recordings.
KEY FINDINGS: To examine seizure thresholds, increasing doses of pilocarpine were administered to adult mice and seizures were scored behaviorally. Significantly fewer STEP knockout mice developed seizures that progressed to the stage of status epilepticus compared to WT mice. To examine potential differences in neural circuits that might account for this finding, seizure-like activity was induced in hippocampal slices. Electrical stimulation of the hippocampal-entorhinal cortex pathway in STEP knockout mice resulted in less activation of the dentate gyrus granule cell layer (GCL), but greater activation of the hilus in STEP knockouts, compared with heterozygous slices.
SIGNIFICANCE: STEP deficiency is associated with higher seizure thresholds. The locus of these effects appears to include the dentate gyrus granule cell layer and hilus.
Authors:
Stephen W Briggs; Jeffrey Walker; Kemal Asik; Paul Lombroso; Janice Naegele; Gloster Aaron
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-04
Journal Detail:
Title:  Epilepsia     Volume:  52     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-05-09     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  497-506     Citation Subset:  IM    
Copyright Information:
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dentate Gyrus / drug effects,  physiopathology
Electroencephalography* / drug effects
Female
Hippocampus / drug effects,  physiopathology*
Male
Mice
Mice, Knockout
Muscarinic Agonists
Patch-Clamp Techniques
Pilocarpine
Protein Tyrosine Phosphatases, Non-Receptor / drug effects,  genetics*
Seizures / chemically induced,  genetics*
Signal Processing, Computer-Assisted*
Tissue Culture Techniques
Grant Support
ID/Acronym/Agency:
K02 MH001527/MH/NIMH NIH HHS; K02 MH001527-10/MH/NIMH NIH HHS; MH01527/MH/NIMH NIH HHS; MH52711/MH/NIMH NIH HHS; R01 MH052711/MH/NIMH NIH HHS; R01 MH052711-17/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Muscarinic Agonists; 01MI4Q9DI3/Pilocarpine; EC 3.1.3.-/Ptpn5 protein, mouse; EC 3.1.3.48/Protein Tyrosine Phosphatases, Non-Receptor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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