HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Glutamate receptor mechanisms in human epileptic dysplastic cortex.

Abstract
Developmental disorders of neuronal migrations in the human brain are referred to as 'cortical dysplasia', and current knowledge of cortical dysplasia is limited to varied pathologic descriptions which lack specific investigations of glutamate receptor mechanisms. In this study, immunocytochemistry was used to study the expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 and AMPA Glu-R2/3 in human brain resected for intractable epilepsy associated with cortical dysplasia. Seventeen patients were studied with batch-matched glutamate subunit reagents on adjacent 30-microm sections. The most striking microscopic abnormalities identified in cresylecht violet stains were cortical dyslaminations, disoriented neurons, and unexpectedly, very dark Nissl body staining of those dysplastic neurons. NMDAR2A/B intensely labeled dysplastic neurons, showing staining in both the cell bodies and dendritic profiles. However, non-dysplastic neurons were not immunoreactive to NMDAR2A/B. Dysplastic neurons were also labeled by antibodies selective to NMDAR1. Both dysplastic neurons and non-dysplastic neurons were immunoreactive to AMPA GluR2/3. Our results suggest that the epileptic hyperexcitability of dysplastic cortical regions may result, at least in part, from the heteromeric coassembly and expressions of NMDAR2A/B subunits with selectively expressed NMDAR1 splice variants in dysplastic neurons. AMPA receptors are probably also essential but not sufficient to explain the 'epileptic' properties of these dysplastic neurons. A longer, detailed report of some of these findings have been previously published (Ying et al., 1998. J. Neuropathol. Exp. Neurol. 57, 47-62).
AuthorsT L Babb, Z Ying, J Hadam, C Penrod
JournalEpilepsy research (Epilepsy Res) Vol. 32 Issue 1-2 Pg. 24-33 (Sep 1998) ISSN: 0920-1211 [Print] Netherlands
PMID9761306 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • NMDA receptor A1
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • glutamate receptor ionotropic, AMPA 3
  • glutamate receptor ionotropic, AMPA 2
Topics
  • Adolescent
  • Adult
  • Aged
  • Alternative Splicing
  • Brain (metabolism, pathology, surgery)
  • Cerebral Cortex (abnormalities, pathology)
  • Child
  • Child, Preschool
  • Epilepsy (genetics, metabolism, surgery)
  • Genetic Variation
  • Humans
  • Middle Aged
  • Neurons (metabolism)
  • Receptors, AMPA (genetics, metabolism)
  • Receptors, Glutamate (genetics, metabolism)
  • Receptors, N-Methyl-D-Aspartate (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: