Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-9-7
pubmed:abstractText
Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
883-93
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16957582-Adolescent, pubmed-meshheading:16957582-Adult, pubmed-meshheading:16957582-Blotting, Western, pubmed-meshheading:16957582-Brain Diseases, pubmed-meshheading:16957582-Cerebral Cortex, pubmed-meshheading:16957582-Child, pubmed-meshheading:16957582-Epilepsy, pubmed-meshheading:16957582-Female, pubmed-meshheading:16957582-Gene Expression, pubmed-meshheading:16957582-Humans, pubmed-meshheading:16957582-Immunohistochemistry, pubmed-meshheading:16957582-Magnetic Resonance Imaging, pubmed-meshheading:16957582-Male, pubmed-meshheading:16957582-Microtubule-Associated Proteins, pubmed-meshheading:16957582-Nerve Tissue Proteins, pubmed-meshheading:16957582-Neuropeptides, pubmed-meshheading:16957582-Protein Subunits, pubmed-meshheading:16957582-Receptors, N-Methyl-D-Aspartate
pubmed:year
2006
pubmed:articleTitle
NMDA receptor composition differs among anatomically diverse malformations of cortical development.
pubmed:affiliation
Molecular Neuroanatomy Lab, Experimental Neurophysiology and Epileptology Unit, Milano, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't