OBJECTIVE: To investigate the effects of chronic in vivo lithium administration on ERK-1/2 signal pathway and the expression of Bcl-2 family proteins, and to elucidate the molecular mechanisms underlying the therapeutic effects of lithium on the manic depression.METHODS: Forty male Wistar rats were evenly divided into 2 groups. One group was treated with 2.4 g/kg of Li2CO3 for 4 weeks. The other group were given with normal chow. By the end of the 4th week, rat brains were removed immediately on decapitation and dissected on ice. The total proteins of rat brain hippocampus and frontal cortex were prepared. Levels of the prylated, active forms of MEK, ERK-1/2, RSK1 and CREB, and the expression levels of Bcl-2 family were assayed by Western Blotting.RESULTS: Lithium increased the activities of MEK, ERK-1/2, RSK1, and CREB, up-regulated the expression of Bcl-2, and down-regulated the expression of Bax in rat brain hippocampus and frontal cortex.CONCLUSION: Chronic in vivo lithium administration activities ERK-1/2 signal pathway and regulates the expression of Bcl-2 family proteins in the central nervous system, which may associate with the therapeutic effects of lithium in the treatment of manic depression.
Animals Bipolar Disorder