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

Ning Ding,Huiling Tian,Shun Wang,Zhigang Li,Jing Jiang

doi:10.3389/fnins.2019.01354

Abstract

BackgroundThe astrocytic phospholipase A2 (PLA2)-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.ObjectiveTo investigate the effect of MA on the astrocytic PLA2-AA pathway in SAMP8 mice hippocampi.MethodsSAMP8 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 chromatography-tandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA2-AA pathway.ResultsCompared 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 PLA2, cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E2 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).ConclusionMA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA2-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.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disease of the central nervous system, characterized by a progressive loss of memory and a cognitive impairment
Acupuncture plays an active role in the clinical efforts against AD and our previous study showed that manual acupuncture (MA) can effectively enhance cerebral blood flow (CBF) in the prefrontal lobes and hippocampi of SAMP8 mice (Ding et al, 2019)
We aimed to elucidate the effect of MA on the astrocytes phospholipase A2 (PLA2)-arachidonic acid (AA) pathway and on the cognitive ability of SAMP8 mice

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease of the central nervous system, characterized by a progressive loss of memory and a cognitive impairment. As the first step in AD development, a decrease in CBF occurs before the appearance of clinical symptoms, which suggests its potential inducing role of AD pathological changes, including the expression of amyloid precursor protein (APP) and tau phosphorylation (Koike et al, 2010; Wang et al, 2010; Salminen et al, 2017) These sustained CBF changes have been associated with cognitive impairment (Hanyu et al, 2010; Leeuwis et al, 2017; Nielsen et al, 2017), and are disease specific (Abdi et al, 2012; Gao et al, 2013; Le Heron et al, 2014) that precede the other AD clinical symptoms (Hays et al, 2016). Ischemia and anoxia, that are caused by a CBF decrease, can directly induce neuronal injury, synaptic dysfunction and promote Aβ accumulation by elevating the expression of the APP and reducing Aβ clearance These events result in neural injuries and neurological disorders, that start the neurodegenerative process (Zlokovic, 2011; Sagare et al, 2012; Nelson et al, 2016).

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