title: Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3.
abstract: BACKGROUND
  The hippocampus is strongly implicated in schizophrenia and, to a lesser degree, bipolar disorder. Proteomic investigations of the different regions of the hippocampus may help us to clarify the basis and the disease specificity of the changes.
  
  
  OBJECTIVE
  To determine whether schizophrenia and bipolar disorder are associated with distinct patterns of differential protein expression in specific regions of the hippocampus.
  
  
  METHODS
  A postmortem comparative proteomic study, including validation of differential expression, was performed. Midhippocampus samples from well-matched groups of 20 subjects with schizophrenia, 20 subjects with bipolar disorder, and 20 control cases from the Stanley Medical Research Institute Array Collection were analyzed.
  
  
  METHODS
  We used laser-assisted microdissection to enrich for tissue from the hippocampal regions and 2-dimensional difference gel electrophoresis to compare protein profiles. Levels of differentially expressed proteins were confirmed by enzyme-linked immunosorbent assay and Western blotting. Hippocampi from haloperidol-treated mice were used to help discriminate drug-associated from disease-associated protein changes.
  
  
  RESULTS
  Across all hippocampal regions, 108 protein spots in schizophrenia and 165 protein spots in bipolar disorder were differentially expressed compared with controls. Sixty-one proteins were differentially expressed in both disorders. One hundred fifty-two of these proteins were identified by mass spectrometry, and they implicated a range of different processes including cytoskeletal and metabolic functions. In both disorders, cornu ammonis regions 2 and 3 were affected to a significantly greater degree than other hippocampal regions. Additionally, numerous proteins showed expression changes in more than 1 region and more than 1 disorder. Validation work confirmed changes in septin 11 and in the expression of proteins involved in clathrin-mediated endocytosis in both schizophrenia and bipolar disorder.
  
  
  CONCLUSIONS
  Overall, similar protein changes were observed in schizophrenia and bipolar disorder and for the first time indicate that the most prominent proteomic changes occur within the hippocampus in cornu ammonis regions 2 and 3. The cytoskeletal protein septin 11 and the cellular trafficking process of clathrin-mediated endocytosis are implicated by our study.
authors.affiliation: Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Föcking
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Jane A
authors.initials: JA
authors.lastname: English
authors.forename: K Oliver
authors.initials: KO
authors.lastname: Schubert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dunn
authors.forename: David R
authors.initials: DR
authors.lastname: Cotter
mesh_terms: D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015153:Blotting, Western; D002966:Clathrin / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D004705:Endocytosis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D042282:Microdissection; D008875:Middle Aged; D040901:Proteomics; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058112:Septins / Q000235:genetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002966:Clathrin; C496549:SEPTIN11 protein, human; D058112:Septins; D006220:Haloperidol