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Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder
- Publication Year :
- 2006
-
Abstract
- Objectives: Schizophrenia is associated with dysfunction of glutamatergic neurotransmission, and several studies have suggested glutamatergic abnormalities in bipolar disorder. Recent data suggest involvement of the NMDA receptor signaling complex, which includes NMDA receptor subunits as well as associated intracellular interacting proteins critical for NMDA receptor assembly, trafficking, and activation; the most well-characterized being PSD93, PSD95, SAP102, and NF-L. Previously, studies from our laboratories have described changes in glutamate receptor subunit transcript and binding site expression in schizophrenia and changes in NMDA receptor binding site expression in bipolar disorder in postmortem brain tissue. In the present work, we focus on the expression of these molecules in hippocampus in schizophrenia and bipolar affective disorder I. Methods: We performed in situ hybridization to assess hippocampal expression of the transcripts encoding NMDA receptor subunits NR1, 2A, 2B, 2C and 2D, and the transcripts for the NMDA receptor associated PSD proteins PSD95, PSD93, NF-L, and SAP102 in subjects with schizophrenia, bipolar affective disorder I, and a comparison group. We also measured [3H]CGP39653 and [3H]MK-801 binding site expression in the hippocampus in schizophrenia. Results: There was a significant decrease in the expression of transcripts for NR1 and NR2A subunits and SAP102 in bipolar disorder. We did not detect any changes in these transcripts or in binding site expression in the hippocampus in schizophrenia. Conclusions: We propose that the NMDA receptor signaling complex, including the intracellular machinery that is coupled to the NMDA receptor subunits, is abnormal in the hippocampus in bipolar disorder. These data suggest that bipolar disorder might be associated with abnormalities of glutamate-linked intracellular signaling and trafficking processes.
- Subjects :
- Male
Psychosis
Bipolar Disorder
Presynaptic Terminals
Hippocampus
Down-Regulation
Glutamic Acid
Binding, Competitive
Receptors, N-Methyl-D-Aspartate
Synaptic Transmission
Article
Glutamatergic
Radioligand Assay
Predictive Value of Tests
mental disorders
medicine
Humans
RNA, Messenger
Molecular Biology
Regulation of gene expression
Binding Sites
General Neuroscience
Nuclear Proteins
Glutamic acid
medicine.disease
Protein Transport
nervous system
Gene Expression Regulation
Schizophrenia
NMDA receptor
Female
sense organs
Neurology (clinical)
Psychology
Postsynaptic density
Neuroscience
Biomarkers
Developmental Biology
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0124236a622de1d48b9873496897c6f4