TY - JOUR
T1 - Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia
AU - Weickert, Cynthia Shannon
AU - Webster, Maree J.
AU - Hyde, Thomas M.
AU - Herman, Mary M.
AU - Bachus, Susan E.
AU - Bali, Geetha
AU - Weinberger, Daniel R.
AU - Kleinman, Joel E.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1093/cercor/11.2.136
DO - 10.1093/cercor/11.2.136
M3 - Article
C2 - 11208668
AN - SCOPUS:0035152440
VL - 11
SP - 136
EP - 147
JO - Cerebral Cortex
JF - Cerebral Cortex
SN - 1047-3211
IS - 2
ER -