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Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice

Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after ch...

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Autores principales: Zhang, Xueying, Gao, Rui, Zhang, Changteng, Teng, Yi, Chen, Hai, Li, Qi, Liu, Changliang, Wu, Jiahui, Wei, Liuxing, Deng, Liyun, Wu, Lining, Ye-Lehmann, Shixin, Mao, Xiaobo, Liu, Jin, Zhu, Tao, Chen, Chan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404588/
https://www.ncbi.nlm.nih.gov/pubmed/37544956
http://dx.doi.org/10.1038/s41392-023-01543-z
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author Zhang, Xueying
Gao, Rui
Zhang, Changteng
Teng, Yi
Chen, Hai
Li, Qi
Liu, Changliang
Wu, Jiahui
Wei, Liuxing
Deng, Liyun
Wu, Lining
Ye-Lehmann, Shixin
Mao, Xiaobo
Liu, Jin
Zhu, Tao
Chen, Chan
author_facet Zhang, Xueying
Gao, Rui
Zhang, Changteng
Teng, Yi
Chen, Hai
Li, Qi
Liu, Changliang
Wu, Jiahui
Wei, Liuxing
Deng, Liyun
Wu, Lining
Ye-Lehmann, Shixin
Mao, Xiaobo
Liu, Jin
Zhu, Tao
Chen, Chan
author_sort Zhang, Xueying
collection PubMed
description Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain. [Image: see text]
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spelling pubmed-104045882023-08-08 Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice Zhang, Xueying Gao, Rui Zhang, Changteng Teng, Yi Chen, Hai Li, Qi Liu, Changliang Wu, Jiahui Wei, Liuxing Deng, Liyun Wu, Lining Ye-Lehmann, Shixin Mao, Xiaobo Liu, Jin Zhu, Tao Chen, Chan Signal Transduct Target Ther Article Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain. [Image: see text] Nature Publishing Group UK 2023-08-07 /pmc/articles/PMC10404588/ /pubmed/37544956 http://dx.doi.org/10.1038/s41392-023-01543-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Xueying
Gao, Rui
Zhang, Changteng
Teng, Yi
Chen, Hai
Li, Qi
Liu, Changliang
Wu, Jiahui
Wei, Liuxing
Deng, Liyun
Wu, Lining
Ye-Lehmann, Shixin
Mao, Xiaobo
Liu, Jin
Zhu, Tao
Chen, Chan
Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title_full Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title_fullStr Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title_full_unstemmed Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title_short Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
title_sort extracellular rnas-tlr3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404588/
https://www.ncbi.nlm.nih.gov/pubmed/37544956
http://dx.doi.org/10.1038/s41392-023-01543-z
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