RESUMO
BACKGROUND: Electron microscopy and biochemical studies indicate that developmental abnormalities in synaptic organization may be present in brains of schizophrenic patients. This study determined whether these synaptic abnormalities are reflected in differential or uniform alterations in the expression of various synaptic protein genes in the left superior temporal gyrus of schizophrenic patients. METHODS: Levels of mRNAs encoding four synaptic vesicle proteins (synaptotagmin I [p65], rab3a, synaptobrevin 1, and synaptobrevin 2) and two synaptic plasma membrane proteins (syntaxin 1A and SNAP-25) were measured postmortem in the left superior temporal gyrus from elderly (58-95 years) schizophrenic patients (n = 14) and age-matched control subjects (n = 9). RESULTS: There were significant negative correlations between age and levels of synaptotagmin I (p65), rab3a, synaptobrevin 1, SNAP-25, and syntaxin 1A mRNAs in schizophrenic patients (-.692 < r < -.517,.003 < p <.030) but not in control subjects. Levels of all six synaptic mRNAs studied were increased in the younger (58-79 years) subgroup of schizophrenic patients compared to control subjects and older (80-95 years) subgroup of schizophrenic patients. CONCLUSIONS: That similar abnormalities were found for mRNAs encoding different synaptic vesicle and synaptic plasma membrane proteins suggests that they reflect overall neurodevelopmental abnormalities in synaptic connectivity in the temporal cortex of schizophrenic patients rather than changes in the number of synaptic vesicles per synapse or abnormalities in a specific synaptic function.
Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Membrana/metabolismo , RNA Mensageiro/metabolismo , Esquizofrenia/metabolismo , Membranas Sinápticas/metabolismo , Vesículas Sinápticas/metabolismo , Lobo Temporal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Primers do DNA/genética , Feminino , Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Qa-SNARE , Proteínas R-SNARE , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Esquizofrenia/genética , Membranas Sinápticas/ultraestrutura , Vesículas Sinápticas/ultraestrutura , Sinaptotagmina I , Sinaptotagminas , Sintaxina 1RESUMO
Synaptic abnormalities have been implicated in schizophrenia. In order to investigate synaptic pathology in schizophrenia, we examined levels of mRNAs encoding synaptophysin, synapsin 1A and synapsin 1B in the left temporal cortex from schizophrenics (n = 24) and from normal control individuals with no history of psychiatric illness (n = 10). Levels of synaptic mRNAs in the left superior temporal and left middle temporal gyrus declined significantly with age in schizophrenics, but not in controls. Dividing the diagnostic groups according to age (below and above 75 years), the data revealed that in "young" schizophrenics (age <75 years) levels of the three synaptic mRNAs in the left superior and left middle temporal gyri were approximately two times higher than in the age-matched controls. In the "old" schizophrenics (age >75 years) the levels of synaptic mRNAs in temporal cortex did not differ from age-matched controls. These findings further support the hypothesis that developmental synaptic abnormalities may be involved in the pathophysiology of schizophrenia.