title: Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia.
abstract: Schizophrenia has been associated with anatomical and functional abnormalities of the dorsolateral prefrontal cortex (DLPFC), which may reflect abnormal connections of DLPFC neurons. We measured mRNA levels of growth-associated protein (GAP-43), a peptide linked to the modifiability of neuronal connections, in post-mortem brain tissue from two cohorts of patients with schizophrenia and controls. Using the RNase protection assay (RPA), we found a significant reduction in GAP-43 mRNA in the DLPFC, but not in the hippocampus, of patients with schizophrenia. With in situ hybridization histo- chemistry (ISHH), performed on a separate cohort, we confirmed the reduction of GAP-43 mRNA in the DLPFC of patients with schizophrenia. We detected reduced GAP-43 mRNA per neuron in layers III, V and VI of patients with schizophrenia compared with normal controls and patients with bipolar disorder. Thus, glutamate neurons in DLPFC of schizophrenic patients may synthesize less GAP-43, which could reflect fewer and/or less modifiable connections than those in normal human brain, and which may be consistent with the deficits of prefrontal cortical function that characterize schizophrenia.
authors.affiliation: Clinical Brain Disorders Branch, IRP/NIMH/NIH, Bldg. 10, Rm. 4N 308, Bethesda, MD 20892-1385, USA. shannowc@intra.nimh.nih.gov
authors.forename: C S
authors.initials: CS
authors.lastname: Weickert
authors.forename: M J
authors.initials: MJ
authors.lastname: Webster
authors.forename: T M
authors.initials: TM
authors.lastname: Hyde
authors.forename: M M
authors.initials: MM
authors.lastname: Herman
authors.forename: S E
authors.initials: SE
authors.lastname: Bachus
authors.forename: G
authors.initials: G
authors.lastname: Bali
authors.forename: D R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: J E
authors.initials: JE
authors.lastname: Kleinman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics; D015331:Cohort Studies; D021983:Cyclophilins / Q000235:genetics; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D019922:GAP-43 Protein; D012333:RNA, Messenger; D021983:Cyclophilins