Conclusions
CA could significantly improve stress-induced depressive disorder, which may be related to regulating the dysfunction of ADPN-FGF9 pathway via activating PPAR-γ in adipocytes.
Methods
In vivo study, the levels of ADPN and FGF9 in both serum and hippocampus tissues, the expressions of ADPN receptor 2 (AdipoR2) in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological changes of hippocampus were determined in 28-day period of chronic unpredictable mild stress (CUMS)-induced depression model of male ICR (Institute of Cancer Research) mice or adipo-/- mice. In vitro study, the level of ADPN and the mRNA expressions of both ADPN and PPAR-γ were determined in mouse 3T3-L1 preadipocytes.
Results
In vivo study, treatment with CA (50 or 100 mg/kg per day) for 21 days markedly suppressed depressive-like behaviors, the elevating levels of FGF9 and decreasing levels of ADPN in both serum and hippocampus tissues, the downregulating protein and mRNA expressions of AdipoR2 in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological injury of hippocampus induced by CUMS in male ICR mice. The antidepressive effects of CA were markedly attenuated in male CUMS-treated adipo-/- mice. In vitro study, incubation with CA (3-30 μmol/L) for 24 h could concentration-dependently upregulate the mRNA expressions of both PPAR-γ and ADPN as well as increase the level of ADPN. The experiments using PPAR-γ-specific inhibitor GW9662 and transient transfection with mutated PPAR-γ-binding site promotor constructs showed that the activation of PPAR-γ mediated CA-induced ADPN expression in adipocytes. Conclusions: CA could significantly improve stress-induced depressive disorder, which may be related to regulating the dysfunction of ADPN-FGF9 pathway via activating PPAR-γ in adipocytes.