Study on the mechanism of scalp-acupoint cluster puncture in improving hippocampal synaptic plasticity by regulating the cAMP/PKA/CREB signaling pathway in APP/PS1 mice

ObjectiveTo observe the effect of scalp-acupoint cluster puncture on hippocampal synaptic plasticity and the activity of cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP response element-binding protein （CREB） signaling pathway in APP/PS1 mice， so as to explore its possible mechanism underlying improvement of Alzheimer’s disease （AD）.MethodsMale APP/PS1 transgenic mice were randomly divided into model， acupuncture， and sham acupuncture groups， with 12 mice in each group. In addition， 12 male C57BL/6 mice with the same genetic background were used as the control group. The mice of the acupuncture group received cluster-needle stimulation at “Baihui”（GV20） and 2 spots （2 mm to GV20 on the left and right sides）， and those of the sham acupuncture group received cluster-needle stimulation at the bilateral hypochondrial non-acupoints. Following insertion， the needles were twisted rapidly for about 1 min， then retained for 30 min in the acupuncture group. The intervention was conducted once a day， for a total of 28 d. The Morris water maze test and Barnes maze test were used to evaluate the mouse’s learning-memory and cognitive ability. The immunohistochemical staining was employed to detect amyloid-β （Aβ） deposition in the hippocampus. The Nissl staining was used to observe the changes of the number of neurons in the hippocampal CA1 area. A transmission electron microscopy was employed to observe the ultrastructure of hippocampal synapses. The Golgi staining was used to observe the dendritic spine density of hippocampal neurons. The protein expressions of cAMP， PKA， CREB， phosphorylated （p）-CREB， postsynaptic density protein 95 （PSD-95）， and synapsin Ⅰ （SYN1） was detected using Western blot.ResultsCompared with the control group， the model group showed a significant increase in the escape latency of Morris water maze test and the latency to enter the target hole of Barnes maze test and the percentage of Aβ-positive area （PPPPPPConclusionScalp-acupoint cluster puncture can improve the learning-memory ability in APP/PS1 mice， which may be associated with its functions in enhancing the hippocampal synaptic plasticity and up-regulating the cAMP/PKA/CREB signaling.