Abstract |
Excessive N-methyl-D-aspartate ( NMDA) signaling is thought to contribute to bipolar disorder symptoms. Lithium and carbamazepine, effective against bipolar mania, are reported in rats to reduce brain transcription of an arachidonic acid selective calcium-dependent cytosolic phospholipase A(2) (cPLA(2)), as well as expression of one of its transcription factors, activator protein (AP)-2. In this study, we determined if chronic administration of NMDA (25 mg/kg i.p.) to rats would increase brain cPLA(2) and AP-2 expression, as these antimanic drugs are known to down-regulate excessive NMDA signaling. Administration of a daily subconvulsive dose of NMDA to rats for 21 days decreased frontal cortex NMDA receptor (NR)-1 and NR-3A subunits and increased cPLA(2) activity, phosphorylation, protein, and mRNA levels. The activity and protein levels of secretory phospholipase A(2) or calcium-independent phospholipase A(2) were not changed significantly. Chronic NMDA also increased the DNA-binding activity of AP-2 and the protein levels of its alpha and beta subunits. These changes were absent following acute (3 h earlier) NMDA administration. The changes, opposite to those found following chronic lithium or carbamazepine, are consistent with up-regulated arachidonic acid release due to excessive NR signaling and may be a contributing factor to bipolar mania.
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Authors | Jagadeesh S Rao, Renee N Ertley, Stanley I Rapoport, Richard P Bazinet, Ho-Joo Lee |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 102
Issue 6
Pg. 1918-1927
(Sep 2007)
ISSN: 0022-3042 [Print] England |
PMID | 17550430
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Retracted Publication)
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Chemical References |
- Antimanic Agents
- DNA-Binding Proteins
- Excitatory Amino Acid Agonists
- NR1 NMDA receptor
- NR3A NMDA receptor
- Protein Subunits
- RNA, Messenger
- Receptors, N-Methyl-D-Aspartate
- Transcription Factor AP-2
- Arachidonic Acid
- N-Methylaspartate
- Phospholipases A
- Group IV Phospholipases A2
- Phospholipases A2
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Topics |
- Animals
- Antimanic Agents
(pharmacology)
- Arachidonic Acid
(metabolism)
- Bipolar Disorder
(drug therapy, metabolism, physiopathology)
- DNA-Binding Proteins
(drug effects, metabolism)
- Drug Administration Schedule
- Excitatory Amino Acid Agonists
(pharmacology)
- Frontal Lobe
(drug effects, metabolism, physiopathology)
- Group IV Phospholipases A2
- Male
- N-Methylaspartate
(pharmacology)
- Phospholipases A
(drug effects, genetics, metabolism)
- Phospholipases A2
- Phosphorylation
- Protein Subunits
(drug effects, metabolism)
- RNA, Messenger
(drug effects, metabolism)
- Rats
- Rats, Inbred F344
- Receptors, N-Methyl-D-Aspartate
(drug effects, metabolism)
- Subcellular Fractions
- Transcription Factor AP-2
(drug effects, metabolism)
- Up-Regulation
(drug effects, physiology)
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