N-Acetyl-L-aspartyl-L-glutamate changes functional and structural properties of rat blood-brain barrier.
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.
Pliss
Lioudmila
L
Institute of Physiology, Academy of Sciences, Prague, Czech Republic.
Jezová
Daniela
D
Mares
Vladislav
V
Balcar
Vladimir J
VJ
St'astný
Frantisek
F
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
D004151:Dipeptides; C120997:NR2A NMDA receptor; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D012709:Serum Albumin; C027172:isospaglumic acid