title: Decreased expression of a 40-kDa catecholamine-regulated protein in the ventral striatum of schizophrenic brain specimens from the Stanley Foundation Neuropathology Consortium.
abstract: The majority of heat shock proteins (HSP) act as molecular chaperones protecting cells from deleterious stress. These proteins are able to inhibit the aggregation of partially denatured proteins and refold them into the correct conformation. They have also been shown to be involved in the pathogenesis of many neurodegenerative and psychiatric disorders. Previous reports from our laboratory have described a 40-kDa catecholamine-regulated heat-shock-like protein (CRP40). This study investigates CRP40 expression in ventral striatal specimens obtained from the Stanley Foundation Neuropathology Consortium (SFNC). CRP40 levels were significantly reduced in schizophrenic patients relative to the control group. However, ventral striatal samples of individuals diagnosed with major depression or bipolar disorder did not show significant changes in the expression of the protein. No differences in CRP40 levels were observed due to age, sex or postmortem interval (PMI). Further analysis of the schizophrenic group revealed that unmedicated and medicated patients showed decreases in ventral striatal CRP40 levels relative to the control group. However, the largest reduction in these levels was seen in unmedicated schizophrenic patients. In addition, relative to the unmedicated individuals, the clozapine- and haloperidol-treated groups showed elevations in ventral striatal CRP40 expression, although not significant. An increase in sample size may clarify this observation. Taken together, these results suggest a functional role of CRP40 in the pathogenesis of schizophrenia.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Gabriele
authors.forename: Victor Z
authors.initials: VZ
authors.lastname: Chong
authors.forename: Giuseppe F
authors.initials: GF
authors.lastname: Pontoriero
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001479:Basal Ganglia / Q000378:metabolism* / Q000503:physiopathology*; D003024:Clozapine / Q000627:therapeutic use; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D014150:Antipsychotic Agents; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; C422207:catecholamine-regulated protein, 40 kDa; D003024:Clozapine; D006220:Haloperidol