Lithium administration affects gene expression of thyroid hormone receptors in rat brain

Even though lithium has received wide attention in the treatment of manic d epressive illness, the mechanisms underlying its mood stabilizing effects a re not understood. Lithium is known to interact with the thyroid axis and c auses hypothyroidism in a subgroup of patients, which compromises its mood stabilizing effects. Since lithium was recently reported to alter thyroid h ormone metabolism in the rat brain, the present study investigated whether these effects were mediated through regulation of thyroid hormone receptor (THR) gene expression. Adult male euthyroid rats were either given a diet c ontaining 0.25% lithium or one without lithium for 14 days. Rats were sacri ficed in the evening and RNA was isolated from different brain regions to q uantitate the isoform specific mRNAs of THRs. Following 14 days of lithium treatment, THR alpha 1 mRNA levels were increased in the cortex and decreas ed in hypothalamus; THR alpha 2 mRNA levels were increased in the cortex an d THR beta mRNA levels were decreased in the hypothalamus. No significant d ifference in the expression of these THR isoforms was observed in the hippo campus or cerebellum. Thus, chronic lithium treatment appeared to regulate THR gene expression in a subtype and region specific manner in the rat brai n. It remains to be determined whether the observed effects of lithium on T HR gene expression are related to its therapeutic efficacy in the treatment of bipolar disorder.