PirB negatively regulates the inflammatory activation of astrocytes in a mouse model of sleep deprivation.

Reactive astrocytes play a potential regulatory role in sleep deprivation (SD). Paired immunoglobulin-like receptor B (PirB) is expressed in reactive astrocytes, suggesting that PirB may participate in regulating the inflammatory response of astrocytes. We used lentiviral and adeno-associated viral approaches to interfere with the expression of PirB in vivo and in vitro. C57BL/6 mice were sleep deprived for 7 days and neurological function was measured via behavioral tests. We found that overexpressed PirB in SD mice could decrease the number of neurotoxic reactive astrocytes, alleviate cognitive deficits, and promote reactive astrocytes tended to be neuroprotective state. IL-1α, TNFα, and C1q were used to induce neurotoxic reactive astrocytes in vitro. Overexpression of PirB relieved the toxicity of neurotoxic astrocytes. Silencing PirB expression had the opposite effect and exacerbated the transition of reactive astrocytes to a neurotoxic state in vitro. Moreover, PirB-impaired astrocytes demonstrated STAT3 hyperphosphorylation which could be reversed by stattic (p-STAT3 inhibitor). Furthermore, Golgi-Cox staining confirmed that dendrite morphology defects and synapse-related protein were significantly increased in PirB-overexpressed SD mice. Our data demonstrated that SD induced neurotoxic reactive astrocytes and contributed to neuroinflammation and cognitive deficits. PirB performs a negative regulatory role in neurotoxic reactive astrocytes via the STAT3 signaling pathway in SD. Copyright © 2023. Published by Elsevier Ltd.

Citation

Liya Li, Yan Mou, Qian Zhai, Chaoying Yan, Xin Zhang, Mengyu Du, Yansong Li, Qiang Wang, Zhaoyang Xiao. PirB negatively regulates the inflammatory activation of astrocytes in a mouse model of sleep deprivation. Neuropharmacology. 2023 Sep 01;235:109571

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PMID: 37146940

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