Malonate produces striatal lesions by indirect NMDA receptor activation.

Abstract 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.