Manual Acupuncture Regulates Behavior and Cerebral Blood Flow in the SAMP8 Mouse Model of Alzheimer's Disease

Abstract

Background: A growing body of evidence has demonstrated that cerebrovascular function abnormality plays a key role in occurrence and worsening of Alzheimer's disease (AD). Reduction of cerebral blood flow (CBF) is a sensitive marker to early perfusion deficiencies in AD. As one of the most important therapies in complementary and alternative medicine, manual acupuncture (MA) has been used in the treatment of AD. However, the moderating effect of MA on CBF remains largely unknown. Objective: To investigate the effect of MA on the behavior and CBF of SAMP8 mice. Methods: SAMP8 mice were randomly divided into the AD, MA, and medicine (M) groups, with SAMR1 mice used as the normal control (N) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 15 consecutive days. The Morris water maze and arterial spin labeling MRI were used to assess spatial learning and memory in behavior and CBF respectively. Results: Compared with the AD group, both MA and donepezil significantly decreased the escape latency (p < 0.01), while also elevating platform crossover number and the percentage of time and swimming distance in the platform quadrant (p < 0.01 or p < 0.05). The remarkable improvement in escape latency in the MA group appeared earlier than the M group, and no significant statistical significance was observed between the N and MA group with the exception of days 5 and 10. The CBF in the prefrontal lobe and hippocampus in the MA group was substantially higher than in the AD group (p < 0.05) with the exception of the right prefrontal lobe, with similar effects of donepezil. Conclusion: Manual acupuncture can effectively improve the spatial learning, relearning and memory abilities of SAMP8 mice. The increase in CBF in the prefrontal lobe and hippocampus could be an important mechanism for the beneficial cognitive effects of MA in AD.

Keywords: Alzheimer’s disease; MRI; Morris water maze; behaviors; cerebral blood flow; hippocampus; manual acupuncture; prefrontal lobe.

FIGURE 1

The results of the visible platform, hidden platform, and reversal trial in each group (n = 10, mean ± SD). (A,B) Comparison of the escape latency and swimming speed of all groups in the visible platform. One-way ANOVA was used. (C) Comparison of the escape latency of all groups in the hidden platform and reversal trial. Two-way ANOVA with repeated measures was used. LSD-t was presented in Supplementary Tables 1, 2. (D) Comparison of the swimming speed of all groups in the hidden platform and reversal trial. Two-way ANOVA with repeated measures was used. P < 0.01, P < 0.05 compared with the N group. P < 0.01 compared with the AD group.

FIGURE 2

The results of the probe trial in each group (n = 10, mean ± SD). (A) Comparison of the platform crossover numbers of all groups. (B,C) Comparison of the percentage of time and swimming distances in the SW quadrant of all groups. (D,E) Comparison of the percentage of time and swimming distances in the NE quadrant of all groups. (F) Comparison of the swimming speed of all groups. (G–J) Swimming trajectories in the N, AD, MA and M groups, the water entry points were shown by black square. One-way ANOVA followed by LSD multiple-range test was used except in the comparison of the platform crossover numbers, which were analyzed by Kruskal–Wallis test. ^∗p represents the post hoc analysis. ^##p < 0.01.

FIGURE 3

The results of the arterial spin labeling (ASL) MRI. (A) Perfusion FAIR-RARE images. (B) CBF images. The bilateral hippocampus and prefrontal lobe are shown by red and green ellipses, respectively.

FIGURE 4

The comparison of the CBF of all groups (n = 10, mean ± SD). (A,B) The bilateral prefrontal lobe. (C,D) The bilateral hippocampus. One-way ANOVA followed by LSD multiple-range test was used except in the comparison of the left prefrontal lobe, which were analyzed by Kruskal–Wallis test. ^∗p represents the post hoc analysis. ^##p < 0.01.