Nature. AIM2 inflammatory small cells affect nervous system development by monitoring DNA damage.

My best friend old Red Riding Hood wrote that neurodevelopment is achieved through high rate of nerve cell proliferation and differentiation and high level of new brain cell death.this process produces a large number of by-products resulting from DNA damage, cell debris and cell death, which can activate the immune system.in innate immune response, the damage of DNA, ATP and mitochondrial pressure produced during nerve development can activate inflammasome, which is a kind of polyprotein complex composed of intracellular nucleic acid receptor NLRP3 or aim2, adaptor protein ASC and protease caspase-1.the activation of inflammatory bodies can produce living caspase-1, promote the production and secretion of inflammatory cytokines IL-1 and IL-18, and gasdermin-d-mediated cell apoptosis [1,2]. Br / > of course, it is not known how inflammation affects the development of the brain.on April 8, 2020, John R Lukens research group from the University of Virginia published an article named aim2 inflammasome surveillance of DNA damage shapes neurodevelopment in the journal Nature. It was found that aim2 inflammasome surveillance of DNA damage shapes neurodevelopment could play a role in the development and maturation of the brain, and the intervention of the function of aim2 inflammasome bodies could lead to abnormal behavior in mice.the authors also found that aim2 inflammasome can maintain central nervous system homeostasis by regulating gastermin-d rather than classic inflammatory factors.both cytokine production and cell death are crucial factors in the development of nervous system [3]. Moreover, at each time point in this process, the important components of inflammatory bodies are highly expressed. Therefore, the author began to focus on the issue of whether the activation of inflammatory bodies affects brain maturation and development and central nervous system function.in order to solve this problem, the authors first studied whether inflammatory bodies are activated during the development of brain nervous system.the authors used ASC reporter mice to track the formation of ASC specks, one of the markers of inflammatory body activation.the authors found that on the fifth day after birth (P5), that is, when high frequency of DNA damage and cell death occurred [4], a large number of ASC aggregation spots appeared in the brain.next, the authors investigated whether the activation of inflammasome affects the function of the central nervous system.the authors used casp1 and casp11 double knockout mice (inflammatory body function deficient mice, also known as ice - / - mice). Through a series of behavioral experiments, we found that the loss of inflammasome function can lead to anxiety symptoms in mice.specifically, ice - / - mice were more indifferent to novel environments than wild-type mice in the elevated plus maze experiments.while in the open field testing, ice - / - mice had increased frequency of urination and defecation.these results indicate that dysfunction of inflammatory bodies can lead to behavioral abnormalities represented by anxiety in mice.in addition, the authors also found that the phenotype of aim2 - / - mice is very similar to that of ice - / - mice. Moreover, it has been reported that aim2 inflammasome can induce DNA damage [5] and play a role in the central nervous system injury model [6]. Therefore, the authors believe that aim2 inflammasome can affect the behavior of mice.next, the authors studied whether DNA damage during nervous system development can activate aim2 inflammasome. the authors found that ASC plaques and markers of DNA damage, γ H2AX and 53BP1, were located in the same cell, and the deletion of aim2 resulted in a sharp decrease of ASC aggregation spots. based on the above results, the authors suggest that DNA damage during neurodevelopment can activate aim2 inflammasome. the activation of inflammasome can lead to the release of inflammatory factors and gasdemen-d-mediated apoptosis. next, the authors investigated whether these two factors were the cause of behavioral abnormalities in mice. the authors found that the loss of IL-1 and IL-18 signaling pathways did not affect the behavior of mice; however, gasdemin-d knockout mice had similar phenotypes to aim2 - / - and ice - / - mice in behavior. these results suggest that the anxiety caused by aim2 inflammasome deletion is caused by the loss of gasdermin-d signaling pathway. next, the authors studied whether the loss of aim2 inflammasome function during the development of nervous system would affect the level of DNA damage in the brain. the authors found that the number of nerve cells and the level of DNA damage in the brain of aim2 - / -, ice - / - and gsdmd - / - mice were significantly increased, and such DNA damage occurred in various brain regions, including the amygdala, which affects fear and anxiety. these results suggest that the activation of aim2 inflammasome and the downstream gasdermin-d signaling pathway are involved in the clearance of nerve cells containing DNA damage in the brain. because the activation of the peripheral immune system also affects the development and maturation of the brain and the behavioral activities of mice [7], finally, the author studied whether the aim2 inflammatory bodies in the brain or the peripheral aim2 inflammatory bodies affect the nervous system development of mice. by fluorescence in situ hybridization, we found that aim2 was mainly expressed in microglia, astrocytes and nerve cells during brain development. microglia are usually defined as immune cells in the brain, and caspase-1-specific knockout mice in CX3CR1 + cells (including microglia) of the central nervous system do not exhibit anxiety similar to aim - / - mice. on the contrary, in mice with caspase-1 knockout in nestin + cells (including nerve cells, astrocytes, etc.), the level of DNA damage in brain was significantly increased, and anxiety symptoms were also observed in behavior. these results indicate that caspase-1 expressed in the central nervous system is one of the determinants of behavioral changes and increased DNA damage in the brain of mice. in conclusion, based on the causal relationship of "DNA damage immune response neurodevelopment", the authors found that DNA damage can activate immune response, activate aim2 inflammatory bodies, thus clearing the damaged nerve cells and protecting mice from neurological diseases. < br / < br / < br / < br / < br / < br / < br / original link: platemaker: Qi sauce slides up, reference 1.fernandes alne MRI, T., Yu, J. 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