title: Alterations in the expression of PSA-NCAM and synaptic proteins in the dorsolateral prefrontal cortex of psychiatric disorder patients.
abstract: Alterations in the structure and physiology of the prefrontal cortex (PFC) have been found in different psychiatric disorders and some of them involve inhibitory networks, especially in schizophrenia and major depression. Changes in the structure of these networks may be mediated by the polysialylated neural cell adhesion molecule (PSA-NCAM), a molecule related to neuronal structural plasticity, expressed in the PFC exclusively by interneurons. Different studies have found that PSA-NCAM expression in the hippocampus and the amygdala is altered in schizophrenia, major depression and animal models of these disorders, in parallel to changes in the expression of molecules related to inhibitory neurotransmission and synaptic plasticity. We have analyzed post-mortem sections of the dorsolateral PFC from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients, to check whether similar alterations occur. PSA-NCAM was found in neuronal somata and neuropil puncta, many of which corresponded to interneurons. PSA-NCAM expression was only reduced significantly in schizophrenic patients, in parallel to a decrease in glutamic acid-decarboxylase-67 (GAD67) and to an increased expression of vesicular glutamate transporter 1 (VGLUT1) in the white matter. Depressed patients showed significant decreases in synaptophysin (SYN) and VGLUT1 expression. Whereas in bipolar patients, decreases in VGLUT1 expression have also been found, together with a reduction of GAD67. These results indicate that the expression of synaptic proteins is altered in the PFC of patients suffering from these disorders and that, particularly in schizophrenia, abnormal PSA-NCAM and GAD67 expression may underlie the alterations observed in inhibitory neurotransmission.
authors.affiliation: Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Dpt., Universitat de València, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gilabert-Juan
authors.forename: Emilio
authors.initials: E
authors.lastname: Varea
authors.forename: Ramón
authors.initials: R
authors.lastname: Guirado
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Blasco-Ibáñez
authors.forename: Carlos
authors.initials: C
authors.lastname: Crespo
authors.forename: Juan
authors.initials: J
authors.lastname: Nácher
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology; D012794:Sialic Acids / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*
chemical_list: D039842:Neural Cell Adhesion Molecule L1; C493464:SLC17A7 protein, human; C569014:SYP protein, human; D012794:Sialic Acids; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; C103469:polysialyl neural cell adhesion molecule; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1