Preventive Electroacupuncture Ameliorates D-Galactose-Induced Alzheimer’s Disease-Like Pathology and Memory Deficits Probably via Inhibition of GSK3β/mTOR Signaling Pathway

Abstract

Acupuncture has been practiced to treat neuropsychiatric disorders for a thousand years in China. Prevention of disease by acupuncture and moxibustion treatment, guided by the theory of Chinese acupuncture, gradually draws growing attention nowadays and has been investigated in the role of the prevention and treatment of mental disorders such as AD. Despite its well-documented efficacy, its biological action remains greatly invalidated. Here, we sought to observe whether preventive electroacupuncture during the aging process could alleviate learning and memory deficits in D-galactose-induced aged rats. We found that preventive electroacupuncture at GV20-BL23 acupoints during aging attenuated the hippocampal loss of dendritic spines, ameliorated neuronal microtubule injuries, and increased the expressions of postsynaptic PSD95 and presynaptic SYN, two important synapse-associated proteins involved in synaptic plasticity. Furthermore, we observed an inhibition of GSK3β/mTOR pathway activity accompanied by a decrease in tau phosphorylation level and prompted autophagy activity induced by preventive electroacupuncture. Our results suggested that preventive electroacupuncture can prevent and alleviate memory deficits and ameliorate synapse and neuronal microtubule damage in aging rats, which was probably via the inhibition of GSK3β/mTOR signaling pathway. It may provide new insights for the identification of prevention strategies of AD.

Experimental Evidence of the Benefits of Acupuncture for Alzheimer's Disease: An Updated Review

“…Yu et al reported that highfrequency EA at 50 Hz, rather than low-or medium-frequency EA, exerted stronger protective effect on synapses (Yu et al, 2018), highlighting the need for further studies of the optimal EA stimulation dose. Our recent findings (Yu et al, 2020) showed that EA alleviated memory deficits, attenuated dendritic spine loss, and rescued neuronal microtubule damage in the hippocampal CA1 area of aging rats, likely via inhibition of the GSK3β/mTOR signaling pathway.…”

Manual therapy regulates oxidative stress in aging rat lumbar intervertebral discs through the SIRT1/FOXO1 pathway

“…Taking into consideration the exact efficacy of MT in alleviating LBP [7,46], we observed the effects of MT on the aging of rat IVDs by pressing and kneading the Shenshu (BL23) points. We selected BL23 points as the MT site because they are located on both sides of the spine, so mechanical loading can directly relax the lumbar muscles, and they have been reported to delay the effects of aging [47][48][49]. Through behavioral testing, we found that the pain tolerance and behavior style of the aged rats undergoing the MT intervention were significantly improved.…”

The Role of Acupuncture Improving Cognitive Deficits due to Alzheimer’s Disease or Vascular Diseases through Regulating Neuroplasticity

“…As the downstream target of GSK3 β , the reactivation of mTOR restored the acidification of the autophagy lysosome, further promoting the autophagy clearance of pathological A β plaque load [ 103 ]. Yu et al found that EA rescued structural and functional synaptic plasticity impairments and memory deficits in AD rat models through the inactivation of GSK3 β /mTOR signaling [ 21 ]. Moreover, β -site amyloid precursor protein cleaving enzyme 1 (BACE1) is the key protein involved in A β peptide generation.…”

“…The p70S6 kinase was phosphorylated by activation of the mammalian target of rapamycin (mTOR) signal pathway, which has been shown to promote neuronal growth and LTP [ 107 , 108 ]. Acupuncture stimulation has been indicated to promote neuroplasticity by regulating the mTOR signal pathway in AD or VaD rats [ 21 , 109 ]. Moreover, it was reported that MA could reverse the learning and memory impairments in an AD mouse model through upregulating eukaryotic Y-box-binding protein (YB-1) expression [ 20 ], which enhanced the conjunction among the synapses and promoted synaptic formation indirectly [ 110 ].…”

“…The mechanisms of acupuncture-mediated neuroplasticity have recently attracted increased interest. Accordingly, acupuncture modulation over several cognition- or aging-related gene expressions [ 20 ], plasticity signaling pathways [ 21 , 22 ], and brain functional connectivities [ 23 ] has been studied. Herein, we review the application of different protocols of acupuncture in animal models and humans, and their effectiveness on neuroplasticity in various sections: neurogenesis and gliogenesis, synaptic plasticity, related proteins and signaling pathways, and brain network connectivity.…”