Ionotropic Glutamate Receptors and Expression of <i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Subunits in Subregions of Human Hippocampus: Effects of Schizophrenia

Gao, Xiaohan; Sakai, Kazuo; Roberts, Rosalinda C.; Conley, Robert R.; Dean, Brian; Tamminga, Carol A.

doi:10.1176/appi.ajp.157.7.1141

Cited by 352 publications

(216 citation statements)

References 66 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…38,67,68 It has therefore been suggested that rather than the receptor itself, expression of interacting PSD molecules may be abnormal in schizophrenia. 1 We found increased expression of transcripts for NF-L in DLPFC, and PSD-95 and PSD-93 in ACC in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

et al. 2006

View full text Add to dashboard Cite

Abnormal expression of the N-Methyl-D-Aspartate (NMDA) receptor and its interacting molecules of the postsynaptic density (PSD) are thought to be involved in the pathophysiology of schizophrenia. Frontal regions of neocortex including dorsolateral prefrontal (DLPFC) and anterior cingulate cortex (ACC) are essential for cognitive and behavioral functions that are affected in schizophrenia. In this study, we have measured protein expression of two alternatively spliced isoforms of the NR1 subunit (NR1 C2 and NR1 C2 0 ) as well as expression of the NR2A-D subunits of the NMDA receptor in DLPFC and ACC in post-mortem samples from elderly schizophrenic patients and a comparison group. We found significantly increased expression of NR1 C2 0 but not of NR1 C2 in ACC, suggesting altered NMDA receptor cell membrane expression in this cortical area. We did not find significant changes in the expression of either of the NR1 isoforms in DLPFC. We did not detect changes of any of the NR2 subunits studied in either cortical area. In addition, we studied expression of the NMDAinteracting PSD molecules NF-L, SAP102, PSD-95 and PSD-93 in ACC and DLPFC at both transcriptional and translational levels. We found significant changes in the expression of NF-L in DLPFC, and PSD-95 and PSD-93 in ACC; increased transcript expression was associated with decreased protein expression, suggesting abnormal translation and/or accelerated protein degradation of these molecules in schizophrenia. Our findings suggest abnormal regional processing of the NMDA receptor and its associated PSD molecules, possibly involving transcription, translation, trafficking and protein stability in cortical areas in schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Relative to other hippocampal subfields, binding assays have shown reduced AMPA [134] and histamine H3 receptor binding [135] in CA2 of patients diagnosed with schizophrenia and bipolar disorder respectively , and together these histological and neurochemical abnormalities may manifest as morphological changes at the structural level [136]. Quite how CA2 dysfunction may contribute to particular positive, negative or cognitive symptoms of schizophrenia remains unclear, but the latter may be linked with altered filtering of mnemonic information in hippocampus.…”

Section: Box 4: Ca2 In Diseasementioning

confidence: 99%

Updating hippocampal representations: CA2 joins the circuit

Jones

McHugh

2011

Trends in Neurosciences

114

106

View full text Add to dashboard Cite

The hippocampus integrates the encoding, storage and recall of memories, binding the spatiotemporal and sensory information that constitutes experience and keeping episodes in their correct context. The rapid and accurate processing of such daunting volumes of continuouslychanging data relies on dynamically assigning different aspects of mnemonic processing to specialized, interconnected networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and CA1. However, differentially processed information ultimately has to be reintegrated into conjunctive representations, and this is unlikely to be achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this Review, we highlight recently discovered anatomical and physiological features that are likely to necessitate updates to the hippocampal circuit diagram, particularly by incorporating the oft-neglected CA2 region.3

show abstract

“…These findings complement other postmortem and structural imaging studies of abnormalities in medial temporal lobe structures of schizophrenics. 93,94 In an attempt to relate rCBF to symptoms, Liddle et al 95 reported that negative symptoms were negatively associated with rCBF in left frontal cortex and left parietal areas. Hallucinations/delusions were positively associated with flow in the left parahippocampal gyrus and the left ventral striatum.…”

Section: Clinical Genetics and Phenotypesmentioning

confidence: 99%

Phenotype of schizophrenia: a review and formulation

2004

View full text Add to dashboard Cite

The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.

show abstract

Ionotropic Glutamate Receptors and Expression of N-Methyl-d-Aspartate Receptor Subunits in Subregions of Human Hippocampus: Effects of Schizophrenia

Cited by 352 publications

References 66 publications

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

Updating hippocampal representations: CA2 joins the circuit

Phenotype of schizophrenia: a review and formulation

Contact Info

Product

Resources

About