title: N-Acetyl-L-aspartyl-L-glutamate changes functional and structural properties of rat blood-brain barrier.
abstract: Intracerebroventricular administration of N-acetyl-L-aspartyl-L-glutamate (NAAG), an agonist at group II metabotropic and NR1/NR2D-containing N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, increased the permeability of the blood-brain barrier (BBB) to serum albumin in the striatum, but produced no similar effects in the entorhinal cortex or in the hippocampal formation. Electron microscopy showed that NAAG, but not its hydrolytic products L-glutamate and N-acetyl-L-aspartate, increased the number of transport vesicles in the hippocampal endothelial cells. Furthermore, immunocytochemistry detected NR2D subunits on hippocampal capillaries. Consequently, NAAG may have influenced the vesicular transport via NMDA receptors. There was, however, no correlation with the regional pattern of BBB changes (increased permeability in the striatum) that, in turn, could not be directly related to the NAAG-induced neurodegeneration described previously in the hippocampus where no significant changes in BBB permeability were detected.
authors.affiliation: Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
authors.forename: Lioudmila
authors.initials: L
authors.lastname: Pliss
authors.forename: Daniela
authors.initials: D
authors.lastname: Jezová
authors.forename: Vladislav
authors.initials: V
authors.lastname: Mares
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Balcar
authors.forename: Frantisek
authors.initials: F
authors.lastname: St'astný
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002196:Capillaries / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012709:Serum Albumin / Q000493:pharmacokinetics
chemical_list: D004151:Dipeptides; C120997:NR2A NMDA receptor; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D012709:Serum Albumin; C027172:isospaglumic acid