Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia

Cereb Cortex. 2001 Feb;11(2):136-47. doi: 10.1093/cercor/11.2.136.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Northern
  • Brain Chemistry / genetics
  • Cohort Studies
  • Cyclophilins / genetics
  • Female
  • GAP-43 Protein / genetics*
  • Gene Expression / physiology
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Prefrontal Cortex / physiopathology*
  • RNA, Messenger / analysis
  • Schizophrenia / physiopathology*


  • GAP-43 Protein
  • RNA, Messenger
  • Cyclophilins