Nature back-to-back text: "cold" myelin actually participated in memory formation, domestic scientists led the completion.

In 1854, Rudolf Virchow coined the word myelin from the Greek word "myelos" and used it to describe the rich, uniform thickness, multi-layer stacked membrane structure around the brain neurons. At that time, he speculated that myelin was secreted by neurons and acted as insulation.after more than a century of research, myelin has gradually gained a deeper understanding. Now it is generally believed that myelin is the lipid on the lateral side of neurons, which plays a protective and insulating role.myelin does not originate from neurons, but is formed by oligodendrocytes.oligodendrocytes were mainly concentrated in the white matter and also expressed in the gray matter.oligodendrocytes produce up to 80 different myelin sheaths on various axons to facilitate the rapid jump conduction of current.in recent years, new functions of myelin sheath have emerged, and more and more evidences support that the plasticity of myelin can affect the function of neuronal circuits.the changes of myelin plasticity in adult central nervous system are mainly caused by degeneration of myelin sheath and increase of adult oligodendrocyte and myelin sheath, which is caused by differentiation of oligodendrocyte precursor cells (OPCS).on February 10, 2020, Nature Neuroscience published myelin generation and diminuted myelin renew contribution to age related defects in memory and preservation of a remote fear memory requirements new myelin The article of formation reveals the role of myelin in aging memory deficit and fear memory, and further enriches the role of myelin sheath.the first article was completed by a research team led by Mei Feng, associate professor of basic medicine of the Third Military Medical University of China.studies have shown that the main change observed during normal aging in non-human primates is not the loss of neurons, but the change of myelin sheath.in order to understand the changes of myelin sheath in the process of aging, the researchers observed the expression of myelin basic protein and mature oligodendrocytes in 4-month-old (adult), 13-month-old (middle-aged) and 18-month-old mice respectively. It was found that the number of myelin sheath and mature oligodendrocytes in motor cortex increased gradually from 4-month-old to 13-month-old, and decreased by 35% at 18-month-old However, the number of oligodendrocyte precursor cells did not change.the newly formed myelin sheath of transgenic mice cspg4creert; MAPT mgfp was further used to label the new myelin sheath. The newly formed myelin sheath still existed in 6-8 month old mice, and decreased significantly in 18 month old mice.compared with 4-month-old mice, the water maze test found that cognitive dysfunction occurred in 13 month old mice, and at the same time, the newly formed myelin sheath in the hippocampal CA1 region of the mice was significantly reduced.these data indicate that cognitive impairment is accompanied by a decrease in myelin sheath during aging.in order to further prove the relationship between myelin sheath and cognitive function, the researchers constructed specific knockout mice: Olig2 is an important transcription factor regulating the differentiation of OPC, which can be specifically knocked out by cspg4creert; MAPT mgfp mice and Olig2 floxed mice, which can inhibit the regeneration of myelin sheath, but does not affect the mature oligodendrocytes.it was further found that even young 4-month-old knockout mice still showed significant learning and memory impairment after 3-day water maze test, which further demonstrated that newborn myelin sheath participated in cognitive function.since the decrease of myelin sheath is accompanied by cognitive dysfunction, whether the enhancement of oligodendrocyte differentiation and myelination can improve the memory function of aged mice. the team previously found that muscarinic acetylcholine receptor 1 (chrm1) can effectively and negatively regulate oligodendrocyte differentiation and myelination. cspg4creert; MAPT mgfp mice and chrm1flowed mice can specifically knock out chrm1 on the new myelin sheath. Surprisingly, this operation stopped the decrease of new myelin sheath in old mice (18 months old) and increased the number of myelin sheaths by about 5 times, which was really a divine operation. What's more, the cognitive ability of chrm1 knockout mice was significantly improved. this paper is in the form of brief communication and has not been studied in detail. However, it was further found that the synaptic density increased in chrm1 knockout mice. previous studies have shown that synaptic decrease is the main cause of cognitive impairment in aging. therefore, the increase of myelin sheath and the increase of synaptic density after chrm1 knockout are unknown. but overall, the data support that inhibition of myelin loss can improve memory function in aging mice. another article was completed by the Mazen a. kheirbek team in the Department of psychiatry, University of California, San Francisco. using edu (thymidine analogue, marking the proliferation phase) and Olig2 (a marker of oligodendrocyte precursor cells), the researchers found that the number of CO labeling of these two markers in the mPFC brain region of mice after fear training increased significantly, indicating that fear training can promote the proliferation and differentiation of oligodendrocyte precursor cells. the increase of oligodendrocytes related to fear memory was only found in the mPFC brain region, and did not exist in the hippocampus, amygdala and other key brain regions highly related to fear. it was further found that these differentiated oligodendrocytes eventually differentiated into mature oligodendrocytes. in the original text, it is not given the specific time for these oligodendrocytes to proliferate and differentiate into mature oligodendrocytes, but this process takes about 4 weeks. in a similar way, the researchers conditionally knocked out the transcription factor myrf of oligodendrocytes to inhibit oligodendrocyte formation and new myelination, while retaining the existing myelin sheath. after one day of fear training, these knockout mice showed obvious rigidity like normal mice, but they still could not show fear behavior even after 30 days of memory retrieval training, which indicated that the long-term memory of knockout mice was impaired, which may be related to the new myelin sheath. under normal circumstances, the number of c-fos in mPFC, amygdala, hippocampus and other brain regions increased significantly after 30 days of memory retrieval experiment after fear training, while the number of neurons activated in these brain regions decreased in knockout mice. Is it said that inhibition of myelin sheath regeneration will affect the activation of neurons? Since the activated neurons labeled with c-fos immunofluorescence technique could not reflect the changes of neuronal activity in real time, the optical fiber recording system was further carried out by injecting calcium indicator of AAV vector into mPFC. It was found that the calcium activity of the knockout mice decreased during the memory retrieval experiment on the 30th day. these results indicate that neuronal activity is disordered after inhibition of myelin formation. mastine fumarate is an antihistamine developed by Sandoz company of Switzerland in the 1960s. It is clinically used to treat various allergic diseases induced by histamine and is one of the best antihistamines recognized in the world. but in recent years, it has been considered as a drug promoting myelination in high-throughput screening. therefore, researchers used the drug to promote myelin regeneration. After 3 weeks of continuous injection of the drug, wild-type mice carried out memory retrieval experiments on the 30th day. It was found that the fear behavior of mice was enhanced, that is to say, fear memory could be enhanced. in addition, the knockout mice did not show long-term memory impairment after injection of the drug, and returned to normal level. it was found that inhibition of myelin regeneration can restore the long-term memory impairment in mice. to summarize these two articles are about the role of myelin regeneration in memory, so that we have a deeper understanding of myelin sheath, which also provides a new strategy for improving memory. although these two articles have sufficient evidence for the involvement of new myelin sheath in memory, neither of them clearly explains why myelin regeneration participates in memory. how the body can improve the social disorder of autism is the key, not just the appearance of fever. References: 1. Myelin generation and diminuted myelin renew contribute to age related defects in memory2. Preservation of a remote fear memory requirements new myelin formation Disclaimer: cover pictures and article pictures are from the network ● previous recommendations (comprehensive report): in the same field, nature withdraws articles first, Science publishes articles later, focusing on synaptic pruning ● what does it mean to dynamically observe AMPA receptors in human body? ● nature: vascular endothelial growth factor promotes brain lymphatic vessels to play an anti nervous system tumor role ● unexpected! The change of cerebral blood flow can induce anxiety