ABSTRACT
OBJECTIVE: In order to identify whether the mechanisms associated with neurotransmitter release are involved in the pathologies of bipolar disorder and schizophrenia, levels of presynaptic [synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin, vesicle-associated membrane protein, dynamin I] and structural (neuronal cell adhesion molecule and alpha-synuclein) neuronal markers were measured in Brodmann's area 9 obtained postmortem from eight subjects with bipolar I disorder (BPDI), 20 with schizophrenia and 20 controls. METHODS: Determinations of protein levels were carried out using Western blot techniques with specific antibodies. Levels of mRNA were measured using real-time polymerase chain reaction. RESULTS: In BPDI, levels of SNAP-25 (p < 0.01) and synaptophysin (p < 0.05) increased. There were no changes in schizophrenia or any other changes in BPDI. Levels of mRNA for SNAP-25 were decreased in BPDI (p < 0.05). CONCLUSION: Changes in SNAP-25 and synaptophysin in BPDI suggest that changes in specific neuronal functions could be linked to the pathology of the disorder.
Subject(s)
Bipolar Disorder/metabolism , Prefrontal Cortex/metabolism , Synaptophysin/metabolism , Synaptosomal-Associated Protein 25/metabolism , Antibodies , Bipolar Disorder/immunology , Cell Adhesion Molecules/immunology , Cell Adhesion Molecules/metabolism , Cell Culture Techniques , Dynamin I/immunology , Dynamin I/metabolism , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prefrontal Cortex/anatomy & histology , Prefrontal Cortex/pathology , Qa-SNARE Proteins/immunology , Qa-SNARE Proteins/metabolism , R-SNARE Proteins/immunology , R-SNARE Proteins/metabolism , RNA, Messenger/immunology , RNA, Messenger/metabolism , Schizophrenia/immunology , Schizophrenia/metabolism , alpha-Synuclein/immunology , alpha-Synuclein/metabolismABSTRACT
To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic(1) (M1R) and muscarinic(4)(M4R) protein and mRNA as well as [(3)H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [(3)H]pirenzepine binding to BA 9 (mean +/- SEM: 151 +/- 15 vs 195 +/- 10 fmol mg(-1) ETE; P< 0.02), but not BA 40 (143 +/- 13 vs 166 +/- 11 fmol mg(-1) ETE), from subjects with schizophrenia. The level of M1R protein (0.11 +/- 0.007 vs 0.15 +/- 0.008 OD; P < 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 +/- 7.0 vs 79 +/- 14 dpm x 10(3) mg(-1) ETE, P < 0.01) and BA 40 (28 +/- 5.9 vs 99 +/- 14, P < 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 +/- 6.6 vs 89 +/- 9.9, P < 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.
