Lithium Carbonate Alleviate Neuronal Apoptosis to Improve Depression Symptoms in Mice by the JNK/c-Jun Signaling Pathway

Abstract

Abstract Objective Lithium is a monovalent cation that was introduced in 1949 by John Cade for the treatment of bipolar disorder，especially for mania.As for mood stabilizer, it should be effective in treatment of depression.To explore lithium alleviate the apoptosis of nerve cells through JNK/ C-Jun signaling pathway and improve the depressive symptoms in depressed mice. Methods 30 male mice were randomly divided into blank control(control) , model group(stress) and drug intervention group(stress+lithium). A model of depression was established by Chronic unpredictable mild stress (CUMS). Mice in stress+lithium group were given lithium from 4th weekend. The behavior of mice were evaluated and Western blot was used to detect expression levels of related proteins. Results Compared with control, stress+lithium group showed a significant decrease depressive symptoms (P< 0.01).Western blotting results show that compared with stress group, protein levels of P-JNK /JNK ,P-C-Jun/C-Jun ,caspase-3 and Bax in PFC of control were significantly increased (P < 0.01), Bcl-2 level significantly decreased (P < 0.01);Compared with the stress group, the protein levels of nerve cells p-JNK/JNK, P-C-Jun/C-Jun, aspase-3 and Bax in prefrontal cortex of mice in stress +lithium group were significantly decreased (P< 0.01), Bcl-2 level increased significantly (P < 0.01). Conclusions Lithium improve depression symptoms by reducing apoptosis of prefrontal cortex nerve cells through JNK/ C-Jun signaling pathway in depressive mice.