Modulatory effects of acupuncture on murine depression-like behavior following chronic systemic inflammation

Abstract

Depression associated with inflammatory immune responses may be an important medical problem from the perspective of quality of life in old age because chronic inflammation is recognized to have a close connection with the aging process. Activated proinflammatory cytokines induce depression-like behavior by stimulating the expression of indoleamine-2,3-dioxygenase, an enzyme catalyzing the conversion of tryptophan to kynurenine, and by reducing brain synaptic activities of serotonin and dopamine. Experimental inoculation of Bacillus Calmette-Guérin vaccine (BCG) in the mouse gradually and continuously elicits chronic inflammation-associated depression-like behavior. Despite extensive use of acupuncture therapy for treating various psychosomatic disorders in the Oriental medicine, an experimental study showing antidepressant-like activity of acupuncture stimulation has not been performed in the inflammation-associated depression-like animal behavior yet. In the present study, the antidepressant-like activity of acupuncture and its mechanism of action were investigated in BCG-inoculated mice. We confirmed that acupuncture stimulation significantly reduced depression-like behavior and that it lowered the kynurenine/tryptophan ratio and raised the serum kynurenic acid/3-hydroxykynurenine ratio. Acupuncture also relieved the hippocampal dopamine level that was lowered by BCG inoculation. Taken together, these findings may indicate that acupuncture has antidepressant-like effects on murine chronic inflammation-associated depression-like behavior due to its modulatory effects on tryptophan-kynurenine metabolism and dopamine metabolism in the brain.