जर्नल ऑफ़ प्रोटियोमिक्स और बायोइनफार्मेटिक्स
खुला एक्सेस

अमूर्त

Comparative Proteome Analysis of Thalamus and Cortex from Rats Subchronically Treated with Kynurenine and Probenecid

Linda Paulson, Linda K. Nilsson-Todd, Klas R. Linderholm, Ann Brinkmalm, Peter S.Eriksson, Göran Engberg and Sophie Erhardt

Research focusing on glutamate as a major contributor to schizophrenia has attained increasing prominence over the past decade. Analogous to an NMDA-receptor hypofunction in schizophrenia, growing evidence suggest that the disease is related to an excess of brain kynurenic acid (KYNA), an endogenous antagonist at the glycine-site of the NMDA receptor. Previous studies have shown tha t MK-801, an NMDA-receptor antagonist with psychotomimetic properties, induces alteration of several genes and protein levels in cortex and thalamus previously found to be changed in the brains of patients with schizophrenia. In the present study, we use p roteomics to investigate whether an increased KYNA turnover in the brain, induced by subchronic treatment of kynurenine and probenecid, w ould interfere with the protein synthesis in the cortex and thalamus in the rat brain. The levels of four proteins in the cortex wer e increased in the group treated with kynurenine and probenecid compared to vehicle-treated controls. The proteins were; 1, Ubiquitin carbo xy- terminal hydrolase L1 (UCHL1), 2, Similar to NADH dehydrogenase, 3, Cytochrome c oxidase and 4, protein with an undetermined identity. No protein changes were observed in the thalamus. Two of these proteins are implicated in mitochondrial energy produc tions and mRNA from one of them – cytochrome c oxidase – has previously been shown to be increased in the cortex from patients with schizophrenia. Present result show that increased turnover of the endogenous NMDA receptor antagonist KYNA is able to affect cortical protein synthesis to a condition as observed in patients with schizophrenia.