The latest Science sub-journal: the division of labor is meticulous! Neurons are "dismembered" by glial cells after they die.

Learn about the latest advances in neuroscience ● click the blue word to focus on us ● individuals in nature compete for survival, and individuals with stronger adaptability survive.in fact, this phenomenon of survival of the fittest also exists at the cellular level.neuronal death always exists in the whole life cycle.neuronal death plays a key role in regulating the number and type of neurons in early development.it may be better to let the neurons with poor function and poor adaptability disappear.cell debris formed after neuron death is removed by professional or non professional "cleaners".if it is not cleaned up timely or incomplete, it will cause a series of immune inflammatory reactions, i.e. developmental disorders in the early stage of life (1) and cognitive impairment (2) in the later stage of life.in the brain, microglia are considered to be the most important phagocytic debris scavenger, and astrocytes can also phagocytize debris, but their ability is far less than that of microglia, so they are called non professional "cleaners".on June 26, 2020, the team of Jaime grutzendler, Department of neuroscience, Yale University, published an article in the journal science advances to reveal how microglia and astrocytes cooperate to efficiently remove neuronal debris (3).in order to observe the death of single neuron at any time and in any position, the research team developed a two-photon chemical apoptosis targeted ablation technology (2photal) in nature communications in 2017, which uses femtosecond pulse laser to focus and bleach nucleic acid binding dye, causing dose-dependent apoptosis of single cell (4).Figure 1 is cited from reference 3.dedicated microglia are cleaning up the garbage of neurons. In this paper, the researchers observed the clearance of neuronal debris in the cortical region using 2phatal technology. It was found that after the death of neurons, multiple microglia and astrocytes rapidly responded and migrated to the dead neurons at the same time for cleaning.but in the end, after fierce competition, only one microglia can completely devour the dead neurons, which once again highlights the professionalism of microglia "cleaner"! What's more surprising is that in addition to the priority of cleaning up the neuronal bodies, microglia also include the removal of axons near neurons, which can be regarded as a "labor model"; in contrast, lazy astrocytes are actually unwilling to move their bodies and only clean up small dendritic fragments.in fact, it is not microglia that are "industrious", astrocytes are "lazy", but they are responsible for different parts and work together to perform their respective duties.in addition, microglia and astrocytes, a specific and cooperative way of cleaning up, also exist in other neuronal death models.so how do microglia and astrocytes quickly recognize dead neurons? The researchers found that tyrosine kinase receptors Axl and MERTK mediate this recognition and phagocytosis.after MERTK knockout, the time for microglia to migrate to the dead neurons was prolonged; Axl knockout did not affect the clearance ability of microglia; the effects of Axl and MERTK knockout on microglia clearance capacity were similar to that of MERTK knockout alone. Br / > this indicates that the microglia play a key role in the process of . How can microglia and astrocytes efficiently and cooperatively clean up neuronal debris? The researchers found that the phagocytic capacity of astrocytes did not change after knocking out MERTK on these two types of cells at the same time; however, after specific removal of MERTK on microglia, the phagocytic capacity of astrocytes was enhanced, but the clearance capacity was still impaired, that is to say, astrocytes could not turn the tide. these studies indicate that astrocytes phagocytize small dendritic fragments and rarely gather around the cell body. by inhibiting the function of microglia, the researchers found that astrocytes were actually close to the cell bodies of neurons and removed the cell bodies in a scattered way, which was quite different from the complete phagocytosis of microglia. to put it simply, this kind of cooperation is "you are strong and I am weak, and you are weak and I am weak. You are the main one", but here "you" refers to microglia and "I" refers to astrocytes. generally speaking, astrocytes are mainly responsible for the cleaning up of small structures, and microglia are responsible for the cleaning of cell bodies and axons after neuronal death. Through this efficient cooperative way, they can quickly remove the fragments of neurons and create a microenvironment conducive to the survival of normal neurons. This cooperation mode mainly depends on MERTK receptors. References: 1. A. A. E. hochreiiter huffford, C. S. Lee, J. M. kinchen, J. A. A. call, A. L. Klibanov, Z. Yan, J. W. Mandell, K. s. ravikandran, phosphotidylserinreceptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497, 263 – 267 (2013) 2. J. I. getchegaray, E.J. J. J. J. J. J. J. J. e., e. J. J. J. J. J. e., e. J. J. J. J. J. J. e., e., e., e. J. J. J., e., e., e. J. J. J. J., J. A. K., Z. ya, Z. elguero, J. A. tran, V. Sinatra, M. B. feany, K. McCall, Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation. J. Neurosci. 36, 3170–3183 (2016)3. Damisah et al. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo，, Sci. Adv. 2020; 6 : eaba32394．R. A. Hill, E. C. Damisah, F. Chen, A. C. Kwan, J. Grutzendler, Targeted two-photon chemical apoptotic ablation of defined cell types in vivo. Nat. Commun. 8, 15837 (2017).