"Memorial Edition" honors neuroscientists: the strongest review of the century-old research process of small glial cells.

One hundred years ago, Spanish scientist P ı o del R ı o-hortega discovered a new cell type in an experiment, which he called microglia, because their somatic cells are very small, much smaller than astrocytes.since then, microglia began to become a member of nerve cells and gradually entered people's vision.scientists who made outstanding contributions to glial cells were a period of vigorous development of Spanish culture and Science in the early 20th century. At that time, ramony Cajal, a Spanish pathologist, histologist and neuroscientist, founded a neuroscience research institute in Madrid and cultivated many famous neuroscientists.in the late 19th century, Cajal believed that neurons and their connections were the basis of brain function, namely the so-called "neuron theory".on the contrary, Camillo Golgi advocated the "network theory" and believed that the brain is a continuous network.now neuron theory has been widely accepted, but at that time, reticular theory was more popular.but interestingly, Cajal and Golgi won the Nobel Prize in physiology in 1906 for their advances in neuroscience.at that time, in addition to the new concept of neuron, German pathologist Rudolf Virchow also discovered "glial cell" in 1856. Later, in 1895, Hungarian researcher Mihaly lenhosse further named this kind of glial cell as astrocyte, which further enriched the type of brain cells.at that time, Cajal was not interested in astrocytes, but began to study astrocytes after Nicola's achu'carro joined his laboratory.by developing new imaging methods, Cajal can clearly describe the morphology of fibrous astrocytes and protoplasmic astrocytes.the development of microglia research from 1919 to 2019 the zigzag path of the birth of the concept of microglia. At that time, a diehard fan of Cajal, R ı'o-hortega, a young researcher from a remote Castile village in Spain, appeared.he entered achu's laboratory and began to systematically develop methods for rendering brain cells. In an experiment, he unexpectedly found that nonpolar cells were actually composed of two different cell types, which he named microglia and interfascicular glia (which he later renamed oligodendrocyte).after unremitting efforts, R ı o-hortega clearly and systematically identified the three main types of glial cells in the brain: astrocytes, oligodendrocytes and microglia. Since then, the world of glial cells has been opened to us.but things are not so smooth, the new term microglia is not accepted by people.at that time, it was Cajal, the scientist most admired by R ı o-hortega, who strongly questioned microglia, which led R ı o-hortega to doubt his own experimental results for a time.there is no love or hatred for no reason in the world.the growing R ı o-hortega laboratory has occupied part of the resources of Cajal laboratory, causing fierce conflicts among their research members.in spite of these objective points of view, R ı o-hortega staining method is indeed better than Cajal, the former can clearly see complex microglia, while the latter can only see the apolar cells.the controversy between R ı o-hortega and Cajal lasted for some time. Until 1924, American neurosurgeon Wilder Penfield had the opportunity to observe Robson's brain slices directly. He was surprised to find that Robertson did not label microglia, but labeled oligodendrocytes.since then, the nomenclature and main findings of R ı o-hortega are widely believed to be correct.in the first review on microglia, R ı o-horteg summarized the field in detail and included in the series of "cytology and cellular pathology of the nervous system" published by Penfield. This English chapter has been highly concerned for decades.John kershman of the Montreal Institute of Neurology first analyzed the origin of microglia in the human brain. He observed the infiltration of microglia during human embryonic development and described the movement path of migrating cells.in PubMed, only 38 articles were published during the 23 years from 1945 to 1968.in contrast, in 2018, an average of one article in the microglia field was published every four days.the research on microglia has gone from cold to hot. The turning point was that the team of Georg kreutzberg carried out the research in Munich in 1968, and the research in this field gradually recovered its vitality.in the 1960s and 1970s, kreutzberg's team developed a new model to study the activation of microglia without peripheral monocyte infiltration.by damaging the facial nerve in the peripheral system, they observed the activation of microglia in the facial nucleus.these microglia are involved in the remodeling of neural circuits and may eat the terminals of synapses.the technology of microglia cell culture in vitro has set off an upsurge of functional research by Dana giulian and Timothy Baker (1986) established the first technology of microglia culture in vitro. They isolated and purified microglia from the brain of early postnatal rats and cultured them, which laid the foundation for the follow-up functional research of microglia.using this in vitro cell technology, it was found that microglia produced superoxide when stimulated by yeast derived dextran.in vitro culture studies also showed that microglia could express mch1, a molecule for immune interaction.subsequently, microglia were identified as the main source of cytokines tumor necrosis factor alpha (TNF-a) and cytokine interleukin-1 β.at the same time, an electrophysiological technique was developed to study microglia cultured in vitro. It was found that microglia expressed a completely different membrane current pattern from macrophages. it has been widely believed that potassium channel activity regulates microglial function. it is generations of researchers who have discovered more functions of microglia by using cell culture technology, so the iceberg of microglia has begun to emerge. microglia has entered the era of in vivo research. Although in vitro cells can be used to study microglia, there is a fatal defect that the cultured cells will never reflect the changes of microglia in the complex environment of the brain. with the appearance of PK11195, a ligand that can bind to peripheral benzodiazepine receptors of microglia, it marks that microglia have officially entered the stage of in vivo research from in vitro. using PK11195, we completed the first study of labeling microglia in human body by positron emission tomography (PET). The results showed that there were "activated" microglia in demyelinating area of two patients with multiple sclerosis. because peripheral benzodiazepine receptors are also expressed in astrocytes, their specificity is low. in 1998, researchers cloned a new type of calcium binding protein, i.e. ion calcium adaptor protein 1 (Iba1), which can completely present the morphology of microglia, and is still considered as the gold standard for labeling microglia. at the end of the 20th century, researchers developed mouse strains carrying green fluorescent protein (GFP) in microglia, and since then, in vivo research has entered a rapid development period. using these visualized mice, it is found that microglia have been monitoring the brain microenvironment. Once damaged, microglia immediately rush to repair, just like human medical doctors. The main functions of microglia in recent 20 years, scientists have focused on the role of microglia in physiology and pathology of the brain. a remarkable feature of microglia is its motility, which can be used for real-time dynamic monitoring of brain microenvironment. in addition, microglia can undergo synaptic pruning, especially during development. in pathological conditions, microglia perform classic immune functions, releasing inflammatory factors and phagocyte debris (apoptotic cells, axons and myelin waste). microglia can be associated with the types of neurons: affect the connection and function of neurons; participate in neural stem cells (NSC) and neurogenesis; promote oligodendrocyte growth, myelin sheath formation, myelin sheath regeneration; promote angiogenesis; astrocytes and blood-brain barrier permeability and so on. conclusion after a century of research, although microglia have been placed at the center of neurobiology research, the function of microglia has not been fully understood. In other words, the current research on microglia may be just the tip of the iceberg. with the continuous development of technology, more functions of microglia will emerge. references; [1] Amanda Sierra, Rosa C. paolicelli, and Helmut Kettenmann, Cien an ≈ OS de microgl ı'a: milestone in a century of microglial research; trends in neurosciences, November, Vol. 42, No. 11 the cover picture and article picture are from the Internet history related article: Science sub Journal: TGF β signal or the key to pathological changes caused by vascular barrier damage in aging process nature: can pressing the on / off key of synapse really switch memory mode? Scientists find the key hub of negative emotions raphe nucleus is more terrible than soreness that lactic acid accumulation destroys hippocampal nerve regeneration! 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