Malonate produces striatal lesions by indirect NMDA receptor activation.
We previously showed that local striatal injections of malonate produce age-dependent excitotoxic lesions. In the present study volumetric analysis confirmed that malonate produces age-dependent striatal lesions. Pretreatment with the non-competitive and competitive NMDA receptor antagonists, MK-801 and LY274614, and with lamotrigine resulted in significant protection in 4-month-old animals. In vivo magnetic resonance imaging of lesion area showed a significant correlation of increasing lesion size and lactate production in rats ranging from 1 to 12 months of age. Histological evaluation showed NADPH-diaphorase neurons were spared. The results provide further evidence that a subtle impairment of energy metabolism may play a role in neurodegenerative diseases.
Henshaw
R
R
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
Jenkins
B G
BG
Schulz
J B
JB
Ferrante
R J
RJ
Kowall
N W
NW
Rosen
B R
BR
Beal
M F
MF
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D007546:Isoquinolines; D008314:Malonates; D016194:Receptors, N-Methyl-D-Aspartate; C070935:LY 274614; D016291:Dizocilpine Maleate; C030290:malonic acid