FGF-2 signaling activation in the hippocampus contributes to the behavioral and cellular responses to puerarin

Abstract Puerarin, a well-studied isoflavone isolated from Pueraria lobata , produces an antidepressant-like effect. Fibroblast growth factor-2 (FGF-2) is essentially required in the central nervous system as it acts as both a neurotrophic or anti-inflammatory regulator for the proliferation, differentiation and apoptosis of neurons. There is evidence that FGF-2 holds great promise for therapeutic intervention for depression. However, nothing was known about the involvement of FGF-2 in the antidepressant-like effect of puerarin. In the present study, the underlying mechanism of puerarin was evaluated in chronic stress induced depressive-like mice. The results indicated that puerarin treatment was effective to attenuate anhedonia and despair behaviors caused by chronic stress, as the sucrose preference and the immobility time were improved by puerarin. In addition, the results demonstrated that puerarin increased the expression of FGF-2 in the hippocampus. On the contrary, SU5402, an FGFR1 inhibitor, infusion into the brain could not only block the antidepressant-like effect of puerarin, but also abolish the effect of puerarin on hippocampal neurogenesis enhancement and neuroinflammation inhibition. Taken together, these findings provide new insights into the mechanism that the antidepressant-like actions of puerarin require FGF-2/FGFR signaling for the regulation of neurogenesis and neuroinflammation.