Reduced GAP-43 mRNA in Dorsolateral Prefrontal Cortex of Patients with Schizophrenia
Links to Fileshttps://academic.oup.com/cercor/article/11/2/136/386103
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Type of Work13 pages
Citation of Original PublicationWeickert, Cynthia Shannon; Webster, Maree J.; Hyde, Thomas M.; Herman, Mary M.; Bachus, Susan E.; Bali, Geetha; Weinberger, Daniel R.; Kleinman, Joel E.; Reduced GAP-43 mRNA in Dorsolateral Prefrontal Cortex of Patients with Schizophrenia; Cerebral Cortex 11(2), pages 136-147(2001); https://academic.oup.com/cercor/article/11/2/136/386103;
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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.
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