Huatuo Zaizao pill ameliorates cognitive impairment of APP/PS1 transgenic mice by improving synaptic plasticity and reducing Aβ deposition

Abstract Background It is well known that Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and synaptic dysfunction play important roles in the pathophysiology of Alzheimer’s disease (AD). The Huatuo Zaizao pill (HT) is a Traditional Chinese Medicine (TCM) that has been used clinically for many years in China, mainly for post-stroke rehabilitation and cognitive decline; however, the mechanism of cognitive function is not clear. In this study, we investigated the effect of HT on hippocampal synaptic function, Amyloid-β (Aβ) deposition in APP/PS1 AD transgenic mice. Method Six-month-old APP/PS1 transgenic (Tg) mice were randomly divided into control, HT-treated, and memantine (MEM)-treated groups. Then, these groups were orally administered vehicle (for the control), HT (0.25 g/kg) and MEM (5 mg/kg) respectively for 4 weeks. The Morris water maze, Novel Object Recognition, and Open field tests were used to assess cognitive behavioral changes. We evaluated the effects of HT on neuronal excitability, membrane ion channel activity, and synaptic plasticity in acute hippocampal slices by combining electrophysiological extracellular tests. Synaptic morphology in the hippocampus was investigated by electron microscopy. Western blotting was used to assess synaptic-associated protein and Aβ production and degrading levels. Immunofluorescence staining was used to determine the relative integrated density. Results HT can ameliorate hippocampus-dependent memory deficits and improve synaptic dysfunction by reversing LTP impairment in APP/PS1 transgenic mice. Moreover, HT reduces amyloid plaque deposition by regulating α-secretase and γ-secretase levels. Conclusion HT can improve the learning and memory function of APP/PS1 transgenic mice by improving synaptic function and reducing amyloid plaque deposition