| First Author | Li S | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 4 | Pages | 111532 |
| PubMed ID | 36288697 | Mgi Jnum | J:330955 |
| Mgi Id | MGI:7380188 | Doi | 10.1016/j.celrep.2022.111532 |
| Citation | Li S, et al. (2022) Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like mice. Cell Rep 41(4):111532 |
| abstractText | 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-kappaB 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. |
