title: Antipsychotic drug use is correlated with CRP40/mortalin mRNA expression in the dorsolateral prefrontal cortex of human postmortem brain specimens.
abstract: Heat shock proteins act as intracellular chaperones by assisting with proper protein folding in response to various cellular stresses. In doing so, these proteins protect the cell from unwanted protein aggregation, which in turn, plays an important role in the pathogenesis of numerous disorders. Previous reports from our laboratory have described a 40 kDa catecholamine regulated heat shock-like protein (CRP40), an alternate gene product of the 70 kDa mitochondrial heat shock protein, mortalin. CRP40 shares an intimate association with dopaminergic activity, specifically as it pertains to dopamine dysregulation in schizophrenia. This study investigates human CRP40/mortalin mRNA expression within dorsolateral prefrontal cortex postmortem specimens from normal control, schizophrenic and bipolar patients obtained from the Stanley Medical Research Institute. Real-time polymerase chain reaction was carried out for all patient samples (n=105; n=35 per group) in a blinded manner. No significant alterations in CRP40/mortalin mRNA expression levels were observed between control, bipolar and schizophrenic patients. However, multiple regression demonstrated a distinct positive correlation between CRP40/mortalin mRNA expression and lifetime use of antipsychotic drugs within the schizophrenic patient profile, after controlling for important confounding factors. Thus, the data suggest that human CRP40/mortalin is modulated by dopaminergic activity and may act to protect neurons from excess catecholamine activity in regions of the brain associated with psychosis.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada. gabriejp@mcmaster.ca
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Gabriele
authors.forename: Giuseppe F
authors.initials: GF
authors.lastname: Pontoriero
authors.forename: Nancy
authors.initials: N
authors.lastname: Thomas
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ferro
authors.forename: Geetha
authors.initials: G
authors.lastname: Mahadevan
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: MacCrimmon
authors.forename: Zdenek B
authors.initials: ZB
authors.lastname: Pristupa
authors.forename: Ram K
authors.initials: RK
authors.lastname: Mishra
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D013223:Statistics as Topic
chemical_list: D014150:Antipsychotic Agents; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C422207:catecholamine-regulated protein, 40 kDa; C080352:mortalin; D004298:Dopamine