Pyruvate protects against 3-nitropropionic acid neurotoxicity in corticostriatal slice cultures

Previously, we have shown that 3-nitropropionic acid (NPA) neurotoxicity in organotypic corticostriatal slice cultures is dependent on glucose and glutamate. Here we studied the neuroprotective potential of agents improving mitochondrial function, including creatine, malate, oxaloacetate, Pyruvate and L-lactate in NPA-treated slice cultures. pyruvate provided the best protection against the loss of glutamic acid decarboxylase activity, depletion of GABA levels, increased propidium iodide uptake and increased glial fibrillary acidic protein levels. ATP levels were significantly reduced by 100 microM NPA (but not by 50 microM) and restored by pyruvate (5 mM). Creatine and L-lactate had no significant protective effect. Protective mechanisms of pyruvate are probably multifold, including stimulation of the citric acid cycle, scavenging and reduction of excitotoxicity.