Alterations in the expression of PSA-NCAM and synaptic proteins in the dorsolateral prefrontal cortex of psychiatric disorder patients

A “double hit” murine model for schizophrenia shows alterations in the structure and neurochemistry of the medial prefrontal cortex and the hippocampus

“…Reduced levels of the GAD67 mRNA in the PFC (Akbarian et al, 1995;Guidotti et al, 2000;Hashimoto et al, 2008;Torrey et al, 2005) and the hippocampus (Thompson Ray et al, 2011) are one of the most consistent findings in postmortem studies of individuals with schizophrenia. Similar decreases in GAD67 protein levels in the PFC and the hippocampus of schizophrenics have been found (Torrey et al, 2005), including those reported recently by our group (Gilabert-Juan et al, 2012). The present results are partially in accordance with the findings in schizophrenic brains, showing a significant decrease of GAD67 protein levels in layers V and VI of the mPFC, although no changes were detected in the hippocampus.…”

“…The addition of PSA to NCAM is mediated by the two polysialyltransferases St8SiaII and St8SiaIV (see Hildebrandt et al, 2010 for review). PSA-NCAM is expressed in a subpopulation of interneurons, both in the PFC and the hippocampus of different mammalian species, including humans (Gilabert-Juan et al, 2012;Gomez-Climent et al, 2011;Mikkonen et al, 1998Mikkonen et al, , 1999Nacher et al, 2002;Varea et al, 2005Varea et al, , 2007b, which have more reduced structural features than those lacking this molecule (Gomez-Climent et al, 2011). Interestingly, both NCAM and ST8SIAII genes have been associated or suggested to be associated with schizophrenia (Arai et al, 2006;Atz et al, 2007;McAuley et al, 2012;Tao et al, 2007), and alterations in the expression of NCAM and PSA-NCAM have been found in postmortem studies of this disorder, including some on the hippocampus and the PFC (Barbeau et al, 1995;Brennaman and Maness, 2010;Gilabert-Juan et al, 2012;Sullivan et al, 2007).…”

RETRACTED: Identification of gene ontologies linked to prefrontal–hippocampal functional coupling in the human brain

“…NRCAM belongs to the cell adhesion molecule (CAM) family of adhesion genes and is located in the middle of a genomic region strongly implicated in schizophrenia etiology and has been associated with schizophrenia in a Korean population (44,45). Altered NRCAM levels have been reported in HC, DLPFC, and amygdala and in the cerebrospinal fluid of patients with schizophrenia (46)(47)(48). NRCAM polymorphisms have also been associated with variation in neurocognitive scores in patients with schizophrenia (49).…”

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

“…This present study is the first to use RNA interference to target the expression of VGLUT1 in a specific brain region in vivo as a novel means of manipulating synaptic glutamate release. Hippocampal expression of VGLUT1 mRNA and protein is decreased in schizophrenia (Eastwood and Harrison, 2005;Sawada et al, 2005;Piyabhan and Reynolds, 2006) and, although striatal deficits have also been reported (Piyabhan and Reynolds, 2006;Nudmamud-Thanoi et al, 2007), cortical changes (which do occur in depression; Gilabert-Juan et al, 2012) are far less robust in schizophrenia (Corti et al, 2007;OniOrisan et al, 2008;Uezato et al, 2009;Eastwood and Harrison, 2010) and appear restricted to specific layers of the prefrontal cortex (Eastwood and Harrison, 2005;Bitanihirwe et al, 2009), whereas the amygdala remains unaffected . The principal finding of the current study is that administration of a VGLUT1-targeting lentiviral shRNA vector into the dorsal hippocampus of Targeting whole-brain VGLUT1 expression using conventional gene knockout strategies results in a 35-41% decrease in transporter levels in heterozygous animals (Tordera et al, 2007;Garcia-Garcia et al, 2009).…”