A large number of literature studies have shown that long-term abuse of alcohol can lead to irreversible changes in brain structure and function.22,23 Especially the hippocampus tissue related to memory storage and processing is more susceptible to neurotoxic damage.24–26 And in most neuropathology, the hippocampus area has been shown to be the most affected brain area.27 So far, electroacupuncture has been widely used in the treatment of brain injury in patients with chronic alcoholism and has achieved good results, but its underlying molecular mechanism has not been fully determined.
The study of Johnson et al.28 showed that patients with chronic alcoholism and cognitive impairment are often accompanied by white matter and gray matter brain structure defects on brain CT. In many studies, the relationship between the degree of brain atrophy and alcohol consumption It is widely known that the modification of synapses in the brain, especially in the hippocampus, may be the cellular mechanism of brain memory storage and learning and memory.29
In the metabolomics results, we found that after electroacupuncture at Baihui and Dazhui points, the lipid metabolism process in the hippocampus area has undergone significant changes, and the lipid metabolites of glycerophospholipids, glycerolipids and fatty acyl in the hippocampus have all occurred A significant change. Glyerophospholipids are a key component of the membrane structure of mammalian mitochondria. Due to their different biological functions, their composition is very different in the different cell types, organelles and inner and outer membranes of mammalian mitochondria.30,31Most glycerophospholipids are synthesized through two synthetic pathways, namely the Kennedy pathway and the CDP-DAG (cytidine diphosphate-diacylglycerol) pathway32. In the CDP-DAG pathway, phospholipid synthesis strongly depends on the transport of phospholipids between the endoplasmic reticulum and mitochondria and between the outer and inner mitochondrial membranes33, and glycerophospholipids are the most abundant type of phospholipids. These lipids are biological Part of the membrane is the active substance on the bile and the membrane surface. Glyerophospholipids also act as messengers in the process of cell signal transmission34, providing stability, fluidity and permeability to the nerve membrane, so they are required to have Intact membrane protein, receptors and normal biological functions of ion channels, electroacupuncture at Baihui and Dazhui points has a very important effect on the regulation of the nervous system and immune system, and has a regulatory effect on organ function, neuroinflammatory response, etc.35Studies have shown that electroacupuncture can inhibit the expression level of pro-inflammatory factors and play a neuroprotective effect. The effectiveness of cognitive improvement in AD and vascular dementia has been confirmed in different clinical and animal studies36–38.Therefore, our research results indicate that electroacupuncture at Baihui and Dazhui points may affect brain function by changing the composition of glycerophospholipids. In fact, changes in the lipid composition of nerve membrane glycerophospholipids have been reported to be related to neurological diseases39. In addition, since the myelin sheath contains the highest content of glycerophospholipids in the meninges40, we speculate that electroacupuncture treatment of chronic alcoholism rats may inhibit most of the changes in glycerophospholipids, thereby reducing the breakage of myelin fibers and preventing neurons More serious injuries.
In experimental studies, we found that chronic alcoholism can significantly change glycerophospholipids and glycerophospholipids-related phospholipids, which indicates that alcohol may activate lipogenesis-related enzymes, thereby affecting lipid synthesis pathways, and electroacupuncture can reduce lipids Abnormal accumulation of metabolites. As we all know, the endoplasmic reticulum membrane is mainly composed of lipids. It is also the central organelle of protein and lipid synthesis, membrane biogenesis, exogenous detoxification, and calcium homeostasis. It is responsible for maintaining various aspects of fatty acid and lipid homeostasis41, and Disorders of lipid metabolism can interfere with the normal operation of endoplasmic reticulum function, the strength of cell membrane structure and the basic functions of organelles, such as mitochondria, Golgi apparatus, and nucleus, causing endoplasmic reticulum stress, and PERK ( Protein kinase RNA-like ER kinase) is activated, which damages memory-related functions42,43. Therefore, electroacupuncture at Baihui and Dazhui points may change the lipid distribution in the hippocampus and reduce the effect of alcohol on nerves in the brain. Damage and inflammatory stress response. At the same time, it also shows that electroacupuncture can inhibit the endoplasmic reticulum stress caused by chronic alcoholism in the brain, maintain the homeostasis and cell function of central cells, and protect learning and memory.
Therefore, we speculate that after 6 weeks of alcohol gavage, the alcohol-induced effect in the hippocampus disrupts lipid metabolism in the brain, leading to oxidative damage to brain DNA, proteins, lipids, and even organelles and mitochondria; on the other hand, for 6 consecutive weeks Weeks of alcohol gavage may cause the up-regulation of acid sphingomyelinase (ASMase) expression. ASMase can induce endoplasmic reticulum stress and activate the lipid pathway by synthesizing ceramide. Ceramide has an important contribution to the structure of cell membranes and exerts many Basic cell processes, including cell growth, proliferation, movement, adhesion, differentiation, aging, and apoptosis. Increased ceramide can lead to lipid toxicity and endoplasmic reticulum stress. It is found in the pathogenesis of several neurodegenerative diseases44–48. In this experiment, the metabonomic analysis results are consistent with the recent research literature. The results show that in the brain tissue of chronic alcoholism, we noticed that the level of ceramide in the hippocampus is up-regulated, suggesting that the brain endoplasmic reticulum may respond to chronic alcoholism. After 6 weeks of intervention with electroacupuncture at Baihui and Dazhui points, electroacupuncture may inhibit the occurrence of the endoplasmic reticulum stress process, thereby reducing the level of ceramide, and changing the metabolic profile to maintain the stability and enhancement of cell membranes. Neuroplasticity protects the integrity of brain tissue from damage and improves learning and memory functions.
In summary, by using metabolomics methods, we found that chronic alcoholism can cause profound changes in hippocampal metabolism. Electroacupuncture at Baihui and Dazhui points can reverse and promote the levels of neurotransmitters and lipid metabolites, suggesting electroacupuncture It can improve the inhibitory state of nerve signal transduction at an early stage, and improve the function of brain neurotransmitter and lipid metabolism. It is of great significance to reveal the pathophysiological mechanism of electroacupuncture intervention in the cognitive impairment of learning and memory in rats with chronic alcoholism.