Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A2 and its transcription factor, activator protein-2
Version of Record online: 13 APR 2007
Journal of Neurochemistry
Volume 102, Issue 6, pages 1918–1927, September 2007
How to Cite
Rao, J. S., Ertley, R. N., Rapoport, S. I., Bazinet, R. P. and Lee, H.-J. (2007), Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A2 and its transcription factor, activator protein-2. Journal of Neurochemistry, 102: 1918–1927. doi: 10.1111/j.1471-4159.2007.04648.x
- Issue online: 1 MAY 2007
- Version of Record online: 13 APR 2007
- Received December 26, 2006; revised manuscript received April 9, 2007; accepted April 9, 2007.
- activator protein-2;
- cytosolic phospholipase A2;
- NMDA receptor-3A
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 A2 (cPLA2), 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 cPLA2 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 cPLA2 activity, phosphorylation, protein, and mRNA levels. The activity and protein levels of secretory phospholipase A2 or calcium-independent phospholipase A2 were not changed significantly. Chronic NMDA also increased the DNA-binding activity of AP-2 and the protein levels of its α and β 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.