The Involvement of Nitric Oxide in Synergistic Neuronal Damage Induced by β-amyloid Peptide and Glutamate in Primary Rat Cortical Neurons

Abnormal extracellular accumulation of β-amyloid (Aβ), the major component of senile plaques in the Alzheimer's brain and the excitatory amino acid glutamate are both considered to be associated with neurodegeneration. We studied whether nitric oxide (NO) was involved in neuronal damage induced by Aβ and glutamate in primary rat cortical neurons. Our results demonstrated that (1) Both neuronal damage and NO production were synergistically induced by Aβ-(25-35) and glutamate; (2) This synergistic neuronal damage induced by Aβ-(25-35) and glutamate was attenuated by selective inhibitors of NO synthase. We propose that cytotoxic characteristics of NO, at least in part, are involved in the synergistic neuronal damage induced by Aβ and glutamate, presumably seen in Alzheimer's brains.