Effects of early intervention with Huannao Yicong formula effective components on behavior and cholinergic system of β-amyloid precursor protein transgenic mice

Abstract

To observe the effects of early intervention with effective components from a Chinese herbal formula (Huannao Yicong formula, HNYCF) on behavior and related indicators of cholinergic system in β-amyloid precursor protein (APP) transgenic mice. Sixty 3-month-old APP695 V717I transgenic mice were randomly divided into model group, high-dose HNYCF group (2.80 g/(kg·d)), low-dose HNYCF group (1.40 g/(kg·d)) and donepezil group (0.65 mg/(kg·d)), with 15 mice in each group. Fifteen non-transgenic mice of the same genetic background were used as normal group. The model group and normal group were fed with equal volume of distilled water by gavage. After 6-month continuous medication, the Morris water maze and the passive avoidance test were used to detect the visual spatial learning and memory ability of each mouse. Then the mice were decapitated and their cerebral cortex and hippocampus were isolated to homogenate by sonication. Contents of acetylcholine (ACh) and acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity in the homogenate were determined by enzyme-linked immunosorbent assay, and protein contents of cerebral cortex and hippocampus were measured by Coomassie brilliant blue method. Compared with the model group, high- and low-dose HNYCF and donepezil hydrochloride all improved spatial learning of APP mice in the Morris water maze. The ratio of swimming distance in the central area in the high-dose HNYCF group was longer than that in the model group (P<0.05). In the passive avoidance test, high- and low-dose HNYCF and donepezil hydrochloride improved memory function of APP mice by improving the escape latency and reducing the number of errors (P<0.05, P<0.01). High- and low-dose HNYCF and donepezil hydrochloride reduced the content of AChE, increased the activity of ChAT (P<0.01, P<0.05) and improved the content of ACh in hippocampus (P<0.05); high- and low-dose HNYCF and donepezil hydrochloride increased the content of ACh in cortex (P<0.05). Donepezil hydrochloride reduced the content of AChE in cortex (P<0.05), however, high- and low-dose HNYCF had no obvious influence (P>0.05). High- and low-dose HNYCF increased the content of ChAT in cortex (P<0.05), whereas donepezil hydrochloride had no obvious influence (P>0.05). Early intervention with HNYCF effective components can improve the learning and memory ability of APP transgenic mice. The mechanism may be related to enhancing the function of cholinergic system.