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 histochemistry (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.
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience