Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like mice. 2022

Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu 210023, China.

The function and regulation of different heterogeneous reactive states of astrocytes in depression remain unclear. Here, we demonstrate that neurotoxic reactive (A1-like) astrocytes are strongly induced, prior to behavioral impairments and dendritic atrophy, in depression-like mice. More interestingly, global or microglia-specific knockout of Nod-like receptor protein 3 (Nlrp3) markedly mitigates A1-like astrocyte induction, whereas astrocyte-specific Nlrp3 depletion is ineffective. Microglial Nlrp3 ablation also alleviates the neuronal dysfunction induced by A1-like astrocytes both in vitro and in vivo. We further show that in microglia the NF-κB pathway activates the NLRP3 inflammasome which in turn activates caspase-1 to induce the secretion of A1 inductors, leading to the production of A1-like astrocytes. Altogether, this study reveals the function of microglial NLRP3 inflammasome in the induction of neurotoxic astrocytes via activating neuroinflammatory caspase-1 pathway in response to chronic stress and suggests a potential therapeutic strategy for depression.

UI MeSH Term Description Entries
D003863 Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. Depressive Symptoms,Emotional Depression,Depression, Emotional,Depressive Symptom,Symptom, Depressive
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001253 Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury. Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D058847 Inflammasomes Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders. Inflammasome,Pyroptosome,Pyroptosomes
D020170 Caspase 1 A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE. ICE Protease,IL-1 beta-Converting Enzyme,Interleukin-1beta Converting Enzyme,CASP1 Caspase,IL-1 beta Convertase,IL1BC Enzyme,Interleukin-1 Converting Enzyme,Pro-Caspase-1,Procaspase-1,Caspase, CASP1,Convertase, IL-1 beta,Converting Enzyme, Interleukin-1,Converting Enzyme, Interleukin-1beta,IL 1 beta Convertase,IL 1 beta Converting Enzyme,Interleukin 1 Converting Enzyme,Interleukin 1beta Converting Enzyme,Pro Caspase 1,Procaspase 1,beta Convertase, IL-1,beta-Converting Enzyme, IL-1
D020258 Neurotoxicity Syndromes Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents. Poisoning, Nervous System,Encephalopathy, Toxic,Nervous System Poisoning,Neurotoxic Disorders,Neurotoxin Diseases,Neurotoxin Disorders,Toxic Encephalitis,Encephalitides, Toxic,Encephalitis, Toxic,Encephalopathies, Toxic,Nervous System Poisonings,Neurotoxic Disorder,Neurotoxicity Syndrome,Neurotoxin Disease,Neurotoxin Disorder,Poisonings, Nervous System,Syndrome, Neurotoxicity,Syndromes, Neurotoxicity,Toxic Encephalitides,Toxic Encephalopathies,Toxic Encephalopathy

Related Publications

Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
August 2023, Progress in neuro-psychopharmacology & biological psychiatry,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
March 2017, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
September 2024, Neural regeneration research,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2019, Science signaling,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2020, Advances in protein chemistry and structural biology,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
July 2018, Biochemical and biophysical research communications,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2017, Frontiers in immunology,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2024, Journal of Alzheimer's disease : JAD,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2022, Journal of immunology research,
Shanshan Li, and Yinquan Fang, and Yihe Zhang, and Mengmeng Song, and Xilin Zhang, and Xiao Ding, and Hang Yao, and Miaomiao Chen, and Yiming Sun, and Jianhua Ding, and Qin Wang, and Ming Lu, and Guangyu Wu, and Gang Hu
January 2017, Scientific reports,
Copied contents to your clipboard!