Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats

Abstract

cDNA microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK-801-treated rats. The rats were divided in two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, four genes were up-regulated and five down-regulated. In group 2, seven genes were up-regulated and six down-regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and gamma-enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c-jun proto-oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)-ribosylation factors, platelet-derived growth factor, fructose-bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+-transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, beta-actin and alpha-enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N-methyl-D-aspartate (NMDA)-receptor antagonist treatment as an animal model of schizophrenia.

Proteomics‐driven progress in neurodegeneration research

“…HSP72 and HSP60 were up-regulated in a rat model of schizophrenia [86,110]. HSP70, HSP90, and HSP27 beta-1 were increased in a rat model of ischemia [68].…”

“…Glyceraldehyde 3-phosphate dehydrogenase showed decreased levels in the schizophrenia brain [66], while increased levels were reported for the DS brain [121]. In the brain of rats treated with an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), changes in the levels of several proteins, HSP60, HSP72, DRP2, aldolase c, malate dehydrogenase, dihydrolipoamide acetyltransferase, guanine deaminase, alpha internexin, and stathmin, were reported [86,110].…”

“…responding increase of catalase or glutathione peroxidase [47]. Reduced expression for SOD1 was observed in a rat animal model of schizophrenia [86].…”

“…Similarly, HSP70 decreased in the brain of rats treated with MK-801 for 8 days and increased in rats treated for 18 days. On the other hand, HSP72 increased in the short-term and decreased in the long-term treatment [86].…”

“…In an animal model of the disease, decreased expression for beta actin and stathmin and increased levels for alpha internexin and dystrophinrelated protein 2 were detected [86]. In the brain of patients with depression, reduced levels were reported for GFAP and DRP2, for the latter also in patients with bipolar disorder [55].…”