RESUMO
There is converging evidence of dendritic spine dysfunction in schizophrenia. In the present study we hypothesized that the expression of key proteins involved in dendritic spine development and stability may be affected in schizophrenia. Postmortem frontal cortex (BA6) from patients with schizophrenia, major depressive disorder, bipolar disorder and healthy controls was processed for glutamate post-synaptic fraction extraction and post-synaptic density purification. Protein expression of the post-synaptic fraction and the post-synaptic density was assessed using immunoprecipitation and Western blotting respectively. The expression of the N-methyl-d-aspartate glutamate receptor (NMDAR) subunit NR2A, post-synaptic density 95 (PSD-95), Ca2+/calmodulin-dependent protein kinase II subunits α and ß (CaMKIIα and ß) were significantly reduced in schizophrenia. A significant decrease in the expression of NR2A was also observed in patients with major depressive disorder relative to controls, but not in patients with bipolar disorder. These results add to existing evidence for disturbed post-synaptic glutamate function and synaptic plasticity in schizophrenia. There may also be subtle disturbances in the post-synaptic glutamatergic function in major depressive disorder.
Assuntos
Proteínas de Membrana/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Plasticidade Neuronal/fisiologia , Córtex Pré-Frontal/metabolismo , Esquizofrenia/metabolismo , Adulto , Proteína 4 Homóloga a Disks-Large/biossíntese , Proteína 4 Homóloga a Disks-Large/genética , Feminino , Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Córtex Pré-Frontal/patologia , Proteínas/genética , Proteínas/metabolismo , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/genética , Esquizofrenia/patologiaRESUMO
PURPOSE: The glutamate N-methyl-D-aspartate (NMDA) receptor and the neurotrophin brain-derived neurotrophic factor have been implicated in the pathophysiology of schizophrenia and depression. Since these psychiatric disorders are common in temporal lobe epilepsy (TLE), a comparison of TLE patients with and without coexisting psychiatric symptoms may be useful to unravel pathophysiologic mechanisms for psychosis or depression. METHODS: We used immunoautoradiography to assess the NR1 NMDA receptor subunit and brain-derived neurotrophic factor in resected TLE hippocampus. RESULTS: No changes relative to comparison controls were found for TLE patients with schizophrenia-like psychosis or depression. Increased NR1 was found in the dentate molecular layer in the dysphoria group and unmedicated depressed patients. CONCLUSIONS: An increase in NR1 protein in the dentate molecular layer suggests an upregulation of NMDA receptors in granule cells in TLE patients with dysphoria and depression. This finding is compatible with the theory that increased NMDA receptor function is involved in the pathogenesis of depression and that antidepressants may act by opposing this mechanism.
