Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, including dementia, insomnia and depression. However, the mechanisms underlying SZRD's improvement in cognitive function remain unclear. In this study, we examined SZRD's effect on APP/PS1 transgenic mice and mechanisms associated with SZRD's action in alleviating neuroinflammation and improving synaptic plasticity.

The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through inhibiting Aβ accumulation and neuroinflammation via the JAK2/STAT3 pathway.

The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/day, in L-SZRD and H-SZRD groups, respectively) for 4 weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect synaptic plasticity. ELISA was applied to assess the expression levels of Aβ1-40 and Aβ1-42 in the hippocampus of mice. Western blot (WB) was employed to test the protein expression level of Aβ1-42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect the involvement of JAK2/STAT3 pathway. Besides, we examined the serum and hippocampal contents of IL-1β, IL-6 and TNF-α through ELISA.

Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (P < 0.05 or 0.01). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum and hippocampal concentrations of IL-6, IL-1β and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (P < 0.05 or 0.01). Conclusions: The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through inhibiting Aβ accumulation and neuroinflammation via the JAK2/STAT3 pathway.