title: Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia.
abstract: We have previously identified differential effects of age on global brain gene expression profiles in subjects with schizophrenia compared to normal controls. Here, we have focused on age-related effects of genes associated with the arachidonic acid-related inflammation pathway. Linear correlation analysis of published microarray expression data reveal strong age- and cell-type- specific-effects on the expression of genes related to the arachidonic acid signaling pathway, which differed in control subjects compared to those with schizophrenia. Using real-time qPCR analysis, we validated age and disease effects of arachidonic acid-related genes in a large cohort of subjects with schizophrenia and matched controls (n=76 subjects in total). We found that levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin-endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects with schizophrenia (> 40years of age) compared to matched normal controls or younger subjects with schizophrenia (< 40years of age). These findings contribute to the accumulating evidence suggesting that inflammatory processes in the CNS contribute to pathophysiology of schizophrenia and further suggest that age may be an important factor in the potential use of anti-inflammatory therapies.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Cristina
authors.initials: C
authors.lastname: Capitao
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000235:genetics*; D015331:Cohort Studies; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C545647:PTGER3 protein, human; D012333:RNA, Messenger; D058308:Receptors, Prostaglandin E, EP3 Subtype; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human