N-acetylaspartylglutamate (NAAG) protects against rat striatal quinolinic acid lesions in vivo.
We examined the effects of N-acetylaspartylglutamate (NAAG), an endogenous peptide thought to be involved in neurotransmission and neuromodulation, on striatal quinolinate lesions, a rodent model of Huntington's disease. We found that NAAG (500 and 1000 nmol) co-injected with quinolinic acid significantly reduced lesion volumes (by 50% and 65%, respectively). A 1000 nmol dose of the non-hydrolyzable analogue, beta-NAAG, also reduced quinolinic acid lesion volumes by 78.4%, indicating that the protection observed was not secondary to cleavage of NAAG into N-acetyl-aspartate (NAA) and glutamate. Likewise, co-injection of both NAA and glutamate (1000 nmol each) with quinolinic acid did not significantly alter the size of lesions. NAAG's protective effect may be mediated through actions on N-methyl-D-aspartate receptors or metabotropic glutamate receptors.
Orlando
L R
LR
Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Luthi-Carter
R
R
Standaert
D G
DG
Coyle
J T
JT
Penney
J B
JB
Young
A B
AB
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries; D004151:Dipeptides / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D017378:Quinolinic Acid / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D004151:Dipeptides; D009479:Neuropeptides; C027172:isospaglumic acid; D017378:Quinolinic Acid