Electroacupuncture decreases cognitive impairment and promotes neurogenesis in the APP/PS1 transgenic mice

Abstract

Background: Alzheimer's disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. The purpose of this study was to investigate whether repeated electroacupuncture (EA) stimulation would improve cognitive function and the pathological features of AD in amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice.

Methods: Cognitive function of APP/PS1 double transgenic mice was assessed using the Morris water maze test before and after EA treatment. Levels of amyloid β-peptide (Aβ) deposits in the hippocampus and cortex were evaluated by immunofluorescence, western blot and enzyme-linked immunosorbent assay. Expression of brain-derived neurotrophic factor (BDNF) was also examined by immunofluorescence and western blot. The neurogenesis was labeled by the DNA marker bromodeoxyuridine.

Results: EA stimulation significantly ameliorated the learning and memory deficits of AD mice by shortening escape latency and increasing the time spent in the target zone during the probe test. Additionally, decreased Aβ deposits and increased BDNF expression and neurogenesis in the hippocampus and cortex of EA-treated AD mice were detected. The same change was detected in wild-type mice after EA treatment compared with wild-type mice without EA treatment.

Conclusions: Repeated EA stimulation may improve cognitive function, attenuate Aβ deposits, up-regulate the expression of BDNF and promote neurogenesis in the APP/PS1 double transgenic mice. This suggests that EA may be a promising treatment for AD.

Figure 1

APP/PS1 mice demonstrated features of cognitive impairment seven months after birth. (A) 7-month-old and 10-month-old APP/PS1 mice showed longer latencies for reaching the platform in the Morris Water Maze test than the wild-type mice. (B) The average swimming speeds among different groups were not significant different. (C) During the probe trail, wild-type mice spent more time in the target quadrant than 7-month-old and 10-month-old APP mice. (n = 6 in each group) (*P < .05 from wild-type mice); (D) Compared with the wild-type mice, total Aβ deposits in the hippocampus and cortex of 7-month-old and 10-month-old APP mice were increased.

Figure 2

Electroacupuncture ameliorated cognitive impairments in APP/PS1 mice. (A) Schematic representation of the experiment protocol. (B) Mice from the APP group showed longer latencies for reaching the platform than those from the APP + EA group. (C) The probe test indicated that the time spent in the target quadrant was increased in the APP + EA group and Con + EA group compared with their non EA-treated counterparts. (D) No significant difference was detected in average swimming speed among all the groups. (n = 6 in each group) (*P < .05 vs. Con group; #P < .05 vs. APP group).

Figure 3

Electroacupuncture suppressed the deposition of Aβ_1-42 in the hippocampus and cortex. With immunofluorescence staining following the EA administration, compared with the APP group, the deposition of Aβ1-42 was significantly decreased in the APP + EA group in the (A) cortex and (B) hippocampus. Bar = 20 μm.

Figure 4

Electroacupuncture suppressed the deposition of Aβ_1-42 in the hippocampus and cortex. ELISA test results revealed that Aβ1-42 depositions from the (A) cortex and (B) hippocampus in the APP + EA group and the Con + EA group were significantly lower than those in their non EA-treated counterparts (n = 5 in each group) (*P < .05 vs. Con group; #P < .05 vs. APP group). (C) Western blot result indicated that the expression of Aβ_1-42 in the Con + EA group was lower than that in Con group. A similar result was detected in the APP + EA group compared with the APP group. (n = 3 in each group) (*P < .05 vs. Con group; #P < .05 vs. APP group).

Figure 5

Electroacupuncture upregulated the expression of BDNF in hippocampus and cortex. Representative double immunofluorescence staining of BDNF (red) and NeuN (green) in the (A) cortex and (B) hippocampus. With EA treatment, BDNF was upregulated in the APP + EA group and Con + EA group compared with their non EA-treated counterparts (*P < .05 vs. Con group; #P < .05 vs. APP group). (C) The protein expression of BDNF was evaluated using western blot. EA significantly up-regulated the expression of BDNF in the APP/PS1 mice and wild-type mice compared with their matched counterparts. Data are means ± SD (n = 5 in each group) (*P < .05 vs. Con group; #P < 0.05 vs. APP group). Bar = 20 μm.

Figure 6

Electroacupuncture enhanced neurogenesis in hippocampal region of APP mice. (A) Representative immunofluorescence of BrdU (red) and Nissl (green) staining in the absence or presence of EA treatment. (B) Quantification of BrdU+/Nissl + cells in the CA1 and DG region. Data are presented as means ± SD (n = 5 in each group) (*P < .05 vs. Con group; #P < .05 vs. APP group).