Identification of a novel lithium regulated gene in rat brain

Differential display PCR was used to identify genes regulated by mood stabilizer lithium in rat cerebral cortex. A differentially displayed lithium regulated gene fragment was isolated in rat cerebral cortex after chronic treatment with lithium (1.69 g/kg, p.o. ) for three weeks. A 1216-nucleotide cDNA for a novel lithium regulated gene (NLRG) was isolated from a rat brain cDNA library with RACE (rapid amplification of 5' cDNA end) PCR using a prime from the differentially displayed NLRG gene fragment. The deduced protein sequence was 321 amino acids long, and shows a significant homology with yeast nitrogen permease regulator 2 (NPR2). NLRG expression induced by lithium was confirmed by Northern and slot blot analysis in rat cerebral cortex and neuroblastomaxglioma NG108-15 cells, respectively. In situ hybridization revealed that chronic treatment with lithium increased NLRG gene expression in frontal cortex and hippocampus, but not in striatum, hypothalamus and thalamus regions of rat brain. These results suggest a novel target for lithium which may be relevant to its mechanism of action.