Li-Hong Kong

Objective Alzheimer’s disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. Results EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT_1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Objective(s): To examine the effect and potential mechanism of electroacupuncture (EA) pretreatment in spatial learning, memory, gut microbiota, and JNK signaling in D-galactose-induced AD-like rats. Materials and Methods: The AD-like rat model was generated by intraperitoneal injection of D-galactose. Morris water maze was used to determine spatial learning and memory ability, Real-time PCR to determine intestinal flora levels, ELISA to determine tryptophan (Trp) and 5-HT levels in the colon and hippocampal tissues, immunofluorescence to determine 5-HT levels in enterochromaffin cells (ECs), and immunoblotting to determine JNK signaling protein levels in hippocampal tissues. Results: Electroacupuncture pretreatment significantly reduced escape latency and prolonged exploration time in the target quadrant, and significantly increased the relative DNA abundance of Lactobacillus and Bifidobacterium. Meanwhile, electroacupuncture pretreatment also reduced colonic 5-HT levels and increased hippocampal 5-HT levels. Moreover, electroacupuncture pretreatment significantly inhibited hippocampal JNK pathway-related protein expression, including 5-HT6R, JNK, p-JUNK, c-JUN, and p-c-Jun. And the combination of GV20 and ST36 was more effective than single acupoints. Conclusion: Electroacupuncture pretreatment improved the learning and memory ability of D-galactose-induced AD-like model rats, changed the gut microbiota composition, and the mechanism may be related to the gut-brain axis and the JNK signaling pathway. In addition, the combination of GV20 and ST36 could further enhance the efficacy.

Background: Acupuncture and acupuncture-related therapies are effective for Alzheimer's disease (AD), therefore, we aimed to compare and rank the interventions that mainly focus on acupuncture-related therapies in the treatment of patients with mild to moderate AD. Methods: We used network meta-analysis to evaluate the direct and indirect evidence shown in randomized controlled trials of AD. The data were analyzed using RavMan manager, Stata, and WinBUGS software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: We analyzed a total of 36 eligible studies, including 2712 patients, involving 14 types of acupuncture-related therapies and comprehensive therapies. For Mini-Mental State Examination (MMSE), acupuncture (ACU) combined with cognitive and memory training (Training) was more effective than ACU, ACU+Chinese herb (CH), ACU+Donepezil (DON), CH, DON, DON+Nimodipine (NIM), Music therapy (Music), NIM, Placebo, and Training (P<0.05), while ACU+CH was batter than CH (P<0.05), and ACU+DON+NIM was better than DON+NIM (P<0.05). For Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog), ACU was more effective than DON and placebo (P<0.05). For Activities of Daily Living (ADL), ACU+DON was better than CH, DON, NIM, and Placebo (P<0.05). For the clinical effectiveness rate, ACU, ACU+CH, ACU+CH+DON, ACU+CH+DON+NIM, ACU+DON, CH, NIM were all more effective than DON+NIM (P<0.05), while ACU and ACU+CH were better than DON (P<0.05). The comprehensive ranking results show that ACU+training and ACU have the highest ranking probability. Conclusion: ACU+Training and ACU may be the best therapies to improve the cognitive function of patients with mild to moderate AD, while the combination of acupuncture-related therapies and other therapies has a higher overall benefit.

Objective(s): We aimed to observe the effects of preventive electroacupuncture (EA) on the microbiota- gut-brain axis and spatial learning and memory deficits and to investigate the possible mechanism using D-galactose (D-gal)-induced aging rats. Materials and Methods: D-gal was intraperitoneally injected to establish the aging model. We used Morris water maze to detect spatial learning and memory function of rats. RT-PCR was applied to test targeted gut microbes. The expression of zonula occludens-1 (ZO-1) and Toll-like receptor 4 (TLR4)/ nuclear factor (NF)-KB pathway proteins were detected by Western blotting. ELISA was employed to evaluate the level of lipopolysaccharides (LPS), diamine oxidase (DAO) and S-100 beta. Additionally, we observed ionized calcium-binding adapter molecule-1 (Iba-1) expression in the hippocampal CA1 area by immunofluorescence. Results: Morris water maze test showed decreased mean escape latency and increased target quadrant time after EA treatment. The gut microbiota composition has been modified in EA treated rats. Molecular examination indicated that expression of ZO-1 was improved and the the concentration of LPS in blood and hippocampus were reduced in EA treated rats. Further, we observed an inhibition of activated microglia and TLR4/NF-KB pathway in EA groups. Conclusion: Preventive EA may alleviate the impairments of the microbiota-gut-brain axis and spatial learning and memory in aging, and the mechanism may be related to the inhibition of TLR4/NF-kB signaling pathway. The combination of acupoints GV20 and ST36 can enhance the therapeutic effect in aging rats.

As the global population ages, the prevalence of Alzheimer's disease (AD), the most common form of dementia, is also increasing. At present, there are no widely recognized drugs able to ameliorate the cognitive dysfunction caused by AD. The failure of several promising clinical trials in recent years has highlighted the urgent need for novel strategies to both prevent and treat AD. Notably, a growing body of literature supports the efficacy of acupuncture for AD. In this review, we summarize the previously reported mechanisms of acupuncture's beneficial effects in AD, including the ability of acupuncture to modulate Aβ metabolism, tau phosphorylation, neurotransmitters, neurogenesis, synapse and neuron function, autophagy, neuronal apoptosis, neuroinflammation, cerebral glucose metabolism, and brain responses. Taken together, these findings suggest that acupuncture provides therapeutic effects for AD.

Summary Senile plaques (SPs) are one of the pathological features of Alzheimer’s disease (AD) and they are formed by the overproduction and aggregation of amyloid-beta (Aβ) peptides derived from the abnormal cleavage of amyloid precursor protein (APP). Thus, understanding the regulatory mechanisms during Aβ metabolism is of great importance to elucidate AD pathogenesis. Recent studies have shown that epigenetic modulation—including DNA methylation, non-coding RNA alterations, and histone modifications—is of great significance in regulating Aβ metabolism. In this article, we review the aberrant epigenetic regulation of Aβ metabolism.

Acupuncture can reduce cognitive deficits in Alzheimer’s disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3β protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3β gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2′-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3β gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017.

The article's abstract is no available.