title: Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia and bipolar disorder.
abstract: BACKGROUND
  We previously observed dendritic spine loss in the dorsolateral prefrontal cortex (DLPFC) from schizophrenia and bipolar disorder subjects. In the current study, we sought to determine if the mRNA expression of genes known to regulate the actin cytoskeleton and spines correlated with spine loss.
  
  
  METHODS
  Five candidate genes were identified using previously obtained microarray data from the DLPFC from schizophrenia and control subjects. The relative mRNA expression of the genes linked to dendritic spine growth and function, i.e. IGF1R, MARCKS, PPP1R9A, PTPRF, and ARHGEF2, was assessed using quantitative real-time PCR (qRT-PCR) in the DLPFC from a second cohort including schizophrenia, bipolar disorder, and control subjects. Functional pathway analysis was conducted to determine which actin cytoskeleton-regulatory pathways the genes of interest interact with.
  
  
  RESULTS
  MARCKS mRNA expression was increased in both schizophrenia and bipolar disorder subjects. PPP1R9A mRNA expression was increased in bipolar disorder subjects. For IGF1R, mRNA expression did not differ significantly among groups; however, it did show a significant, negative correlation with dendrite length. MARCKS and PPP1R9A mRNA expression did not correlate with spine loss, but they interact with NMDA receptor signaling pathways that regulate the actin cytoskeleton and spines.
  
  
  CONCLUSIONS
  MARCKS and PPP1R9A might contribute to spine loss in schizophrenia and bipolar disorder through their interactions, possibly indirect ones, with NMDA signaling pathways that regulate spine structure and function.
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: gkonopaske@mclean.harvard.edu.
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Konopaske
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Sivan
authors.initials: S
authors.lastname: Subburaju
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Francine M
authors.initials: FM
authors.lastname: Benes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D013223:Statistics as Topic; D055815:Young Adult; D000099273:Neurabins
chemical_list: D014150:Antipsychotic Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099273:Neurabins; C000619710:MARCKS protein, human; C000619712:Marcks protein, rat
keywords: Actin cytoskeleton; Bipolar disorder; Dorsolateral prefrontal cortex; Postmortem; Schizophrenia; qRT-PCR