Abnormal expression of post-synaptic proteins in prefrontal cortex of patients with schizophrenia

• Published in: Neuroscience letters Vol. 745; p. 135629
• Main Authors: Matas, Emmanuel, John Francis William, Deakin, Toro, Carla Tatiana
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 06.02.2021
• Subjects: Adult; Disks Large Homolog 4 Protein - biosynthesis; Disks Large Homolog 4 Protein - genetics; Female; Gene Expression; Glutamate synapse; Human prefrontal cortex; Humans; Male; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Middle Aged; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neuronal Plasticity - physiology; Post-synaptic density; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Protein expression; Proteins - genetics; Proteins - metabolism; Receptors, N-Methyl-D-Aspartate - biosynthesis; Receptors, N-Methyl-D-Aspartate - genetics; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; Schizophrenia - pathology; Human prefrontal cortex; Schizophrenia; Protein expression; Post-synaptic density; Glutamate synapse
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.135629

•We extract glutamatergic post-synaptic densities (PSD) from human frontal cortex.•We confirmed PSD purity using electron microscopy and Western blotting.•We compared protein expression within samples between psychiatric disorders and comparison controls.•We found disrupted expression of glutamate signalling proteins in schizophrenia and depression. 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 β (CaMKIIα and β) 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.