Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

Abstract

Background: The astrocytic phospholipase A 2 (PLA 2 )-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer's disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive.Objective: To investigate the effect of MA on the astrocytic PLA 2 -AA pathway in SAMP8 mice hippocampi.Methods: SAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 µg/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory. Immunofluorescence staining, western blot and liquid chromatographytandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA 2 -AA pathway.Results: Compared with that in the Rc group, the escape latency in the Pc group significantly increased (p < 0.01); whereas, the platform crossover number and percentage of time and swimming distance in the platform quadrant decreased (p < 0.01). The hippocampal expression of PLA 2 , cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E 2 and epoxyeicosatrienoic acids of the Pc group was drastically higher than that in the Rc group (p < 0.01). These changes were reversed by MA and donepezil (p < 0.01 or p < 0.05). Frontiers in Neuroscience | www.frontiersin.org February 2020 | Volume 13 | Article 1354 Ding et al. Acupuncture Regulates PLA 2 -AA PathwayConclusion: MA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA 2 -AA pathway. We propose that the increase of the arterial tone, which is induced by the inhibition of vasodilatory pathway, may be a reason for the beneficial effect of MA on CBF.Keywords: manual acupuncture, Alzheimer's disease, astrocyte, hippocampus, phospholipase A 2 , arachidonic acid, cerebral blood flow absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Benign regulation of the gut microbiota: The possible mechanism through which the beneficial effects of manual acupuncture on cognitive ability and intestinal mucosal barrier function occur in APP/PS1 mice

“…The escape latency on days 2–5 and the platform crossover number of the Ac group were drastically different from those of the Cc group, demonstrating that the cognitive ability of APP/PS1 mice was significantly reduced, which was in line with the pathological changes of the AD cognitive decline ( Jaroudi et al, 2017 ). MA and probiotics markedly reversed the aforementioned changes, indicating that both MA and probiotics could effectively improve the cognitive ability of APP/PS1 mice, which was consistent with our previous study ( Chen et al, 2017 ; Ding et al, 2019a ). Notably, the significant decline in the escape latency of the Am group occurred earlier than that of the Ap group, suggesting that the improvement in the learning ability of APP/PS1 mice induced by MA was superior to that induced by probiotics to a certain extent.…”

“…Our previous work confirmed that manual acupuncture (MA) plays an important role in the treatment of AD ( WuLi et al, 2021 ). MA can effectively improve the cognitive function and delay the pathological process of AD through the effects of anti-inflammation ( Jiang et al, 2018 ; Ynag et al, 2021 ), the regulation of energy metabolism ( Liu et al, 2017 ; Xu et al, 2020 ), and the regulation of cerebral blood flow ( Ding et al, 2019a , b ). Recently, the correlation between the microbiota–gut–brain axis and the pathogenesis and development of AD has become gradually clear, becoming a new target for the prevention and treatment of AD.…”

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The unbalanced reorganization of weaker functional connections induces the altered brain network topology in schizophrenia

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