Xingnaojing injection improves Aβ1-42-induced memory deficit in mice by altering of excitatory amino acid toxicity and synaptic plasticity

Abstract

Alzheimer’s disease (AD), the widespread type of dementia, is characterized by depositions of senile plaques composed of insoluble amyloid β (Aβ) peptides, and neurofibrillary tangles. It causes progressive degeneration of synaptic plasticity and leads to memory loss and cognition impairment. Abnormal changes in synaptic structure and excitatory amino acid toxicity occurred in early stage in AD and are associated with decreased cognitive function. Xingnaojing (XNJ), a well-known prescription in traditional Chinese medicine, has been used for treatment of stroke in China. In this research, mice were randomly divided into 4 groups: control, Aβ1-42 injected (Aβ) and Aβ1-42 injected with two doses of XNJ (low-dose, high-dose) administration groups. We performed bilateral intra-CA1 injection of Aβ1-42 except control group. Behavioral results showed that the mice treatment with high-dose of XNJ group has a longer exploration time for New object recognition (NOR) and more crossing platform times for Morris water maze (MWM) compared with Aβ group. The expression of MAP-2 was increased by administration of XNJ in immunofluorescence results. Golgi staining showed that XNJ can improve dendritic spine density of damaged neurons. It also increased the protein levels of GAP-43, PSD-95, NR2b, p-AKT/AKT and p-mTOR/mTOR in the brain tissues compared with Aβ group in the Western blot (WB). Our results indicated that XNJ exhibited a protective effect against excitatory amino acid toxicity and synaptic plasticity via AKT/mTOR signal pathway in mice with Aβ1-42-induced memory deficit. These results provided evidences for the novel and potential application of XNJ for the treatment of AD.