Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia.
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.
Weickert
C S
CS
Clinical Brain Disorders Branch, IRP/NIMH/NIH, Bldg. 10, Rm. 4N 308, Bethesda, MD 20892-1385, USA. shannowc@intra.nimh.nih.gov
Webster
M J
MJ
Hyde
T M
TM
Herman
M M
MM
Bachus
S E
SE
Bali
G
G
Weinberger
D R
DR
Kleinman
J E
JE
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*
D019922:GAP-43 Protein; D012333:RNA, Messenger; D021983:Cyclophilins