Changes in the brain protein levels following administration of kainic acid

Kainic acid (KA), a potent neurotoxin and excitatory amino acid, leads to d erangements and modulation of brain proteins. No global brain protein expre ssion pattern induced by KA-treatment has been reported yet. We therefore s tudied the effect of systemic KA administration on the levels of brain prot eins. Rats were injected placebo or KA intraperitoneally and brain was take n after one week. The mitochondrial and cytosolic fractions of the brain pr oteins were analyzed by proteomics technologies and the levels of selected proteins were quantified using specific software. Heat shock protein HSP 27 was exclusively detected in brains of animals treated with KA, whereas the glucose regulated protein GRP 78 was downregulated. The levels of neurofil aments and alpha-internexin were significantly decreased and a fragment of tubulin alpha-1 chain was manifold increased in KA-brains. The mitochondria l enzymes dihydrolipoamide dehydrogenase, ATP synthase beta chain and isoci trate dehydrogenase were reduced and pyruvate kinase Mi was increased follo wing KA treatment. We conclude that the concomitant determination of the br ain proteins indicates altered regulation of heat shock proteins, neuronal death, cytoskeletal disruption, and mitochondrial derangement by systemic K A administration. This report confirms and extends previous studies on the effect of KA on the expression of brain proteins and suggests that our anal ytical system can serve as a model for neurotoxicological, neurobiological, and neuropathological proteome studies.