Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients' brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.