Toll 样受体 2 在吗啡诱导的小鼠小胶质细胞激活中的必需作用。
Essential role of toll-like receptor 2 in morphine-induced microglia activation in mice.
机构信息
Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
出版信息
Neurosci Lett. 2011 Feb 1;489(1):43-7. doi: 10.1016/j.neulet.2010.11.063. Epub 2010 Dec 2.
Abstract
Opioids are powerful pain relievers, but also potent inducers of dependence and tolerance. Chronic morphine administration (via subcutaneous pellet) induces morphine dependence in the nucleus accumbens, an important dependence region in the brain, yet the cellular mechanisms are mostly unknown. Toll-like receptor 2 (TLR2) plays an essential function in controlling innate and inflammatory responses. Using a knockout mouse lacking TLR2, we assessed the contribution of TLR2 to microglia activation and development of morphine dependence. We report here that mice deficient in TLR2 inhibit morphine-induced the levels of microglia activation and proinflammatory cytokines. Moreover, in TLR2 knockout mice the main symptoms of morphine withdrawal were significantly attenuated. Our data reveal that TLR2 plays a critical role in morphine-induced microglia activation and dependence.
摘要
阿片类药物是强效止痛药，但也是导致依赖和耐受的强效诱导剂。慢性吗啡给药（通过皮下植入丸）会在大脑中重要的依赖区域伏隔核中诱导吗啡依赖，但细胞机制在很大程度上尚不清楚。 Toll 样受体 2（TLR2）在控制先天和炎症反应中起着至关重要的作用。使用缺乏 TLR2 的基因敲除小鼠，我们评估了 TLR2 对小胶质细胞激活和吗啡依赖发展的贡献。我们在这里报告，缺乏 TLR2 的小鼠抑制了吗啡诱导的小胶质细胞激活和促炎细胞因子的水平。此外，TLR2 基因敲除小鼠的吗啡戒断的主要症状明显减轻。我们的数据表明，TLR2 在吗啡诱导的小胶质细胞激活和依赖中起着关键作用。
相似文献
1
Essential role of toll-like receptor 2 in morphine-induced microglia activation in mice.
Neurosci Lett. 2011 Feb 1;489(1):43-7. doi: 10.1016/j.neulet.2010.11.063. Epub 2010 Dec 2.
2
Protective effects of atorvastatin against morphine-induced tolerance and dependence in mice.
Brain Res. 2017 Feb 15;1657:333-339. doi: 10.1016/j.brainres.2016.12.028. Epub 2017 Jan 3.
3
Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.
Neurochem Res. 2023 Dec;48(12):3597-3609. doi: 10.1007/s11064-023-03998-6. Epub 2023 Aug 10.
4
Impact of Morphine withdrawal on genes related to the TLR2 pathway expressed in the Prefrontal Cortex.
Sci Prog. 2024 Jul-Sep;107(3):368504241264994. doi: 10.1177/00368504241264994.
5
Toll-like receptor 2 is required for opioids-induced neuronal apoptosis.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):426-30. doi: 10.1016/j.bbrc.2009.11.074. Epub 2009 Nov 13.
6
Fibrillar amyloid-beta peptides activate microglia via TLR2: implications for Alzheimer's disease.
J Immunol. 2008 Nov 15;181(10):7254-62. doi: 10.4049/jimmunol.181.10.7254.
7
Role of the guanine nucleotide binding protein, Gα in the development of morphine tolerance and dependence.
Psychopharmacology (Berl). 2018 Jan;235(1):71-82. doi: 10.1007/s00213-017-4742-2. Epub 2017 Oct 3.
8
Morphine inhibits murine dendritic cell IL-23 production by modulating Toll-like receptor 2 and Nod2 signaling.
J Biol Chem. 2011 Mar 25;286(12):10225-32. doi: 10.1074/jbc.M110.188680. Epub 2011 Jan 18.
9
Microglial activation by microbial neuraminidase through TLR2 and TLR4 receptors.
J Neuroinflammation. 2019 Dec 2;16(1):245. doi: 10.1186/s12974-019-1643-9.
10
Corilagin attenuates morphine-induced BV2 microglial activation and inflammation via regulating TLR2-mediated endoplasmic reticulum stress.
J Toxicol Sci. 2023;48(7):387-398. doi: 10.2131/jts.48.387.
引用本文的文献
1
Increased LPS-induced fever and sickness behavior in adult male and female rats perinatally exposed to morphine.
Brain Behav Immun. 2025 May;126:38-52. doi: 10.1016/j.bbi.2025.01.019. Epub 2025 Feb 3.
2
Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats.
Transl Psychiatry. 2024 Dec 19;14(1):500. doi: 10.1038/s41398-024-03203-4.
3
Alterations in Circular RNAs circOprm1 and circSerpini in the Striatum are Associated with Changes in Spatial Working Memory Performance after Morphine Dependence and Withdrawal in Rats.
Neurochem Res. 2024 Nov 19;50(1):20. doi: 10.1007/s11064-024-04284-9.
4
Impact of Morphine withdrawal on genes related to the TLR2 pathway expressed in the Prefrontal Cortex.
Sci Prog. 2024 Jul-Sep;107(3):368504241264994. doi: 10.1177/00368504241264994.
5
Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.
Pharmacogenomics J. 2024 Jun 1;24(3):18. doi: 10.1038/s41397-024-00339-w.
6
Progress in the study of intestinal microbiota involved in morphine tolerance.
Heliyon. 2024 Feb 29;10(6):e27187. doi: 10.1016/j.heliyon.2024.e27187. eCollection 2024 Mar 30.
7
The Inflammation/NF-κB and BDNF/TrkB/CREB Pathways in the Cerebellum Are Implicated in the Changes in Spatial Working Memory After Both Morphine Dependence and Withdrawal in Rat.
Mol Neurobiol. 2024 Sep;61(9):6721-6733. doi: 10.1007/s12035-024-03993-0. Epub 2024 Feb 12.
8
Microglial inflammation modulates opioid analgesic tolerance.
J Neurosci Res. 2023 Sep;101(9):1383-1392. doi: 10.1002/jnr.25199. Epub 2023 Apr 26.
9
A cAMP-Related Gene Network in Microglia Is Inversely Regulated by Morphine Tolerance and Withdrawal.
Biol Psychiatry Glob Open Sci. 2022 Apr;2(2):180-189. doi: 10.1016/j.bpsgos.2021.07.011. Epub 2021 Aug 5.
10
Inflammatory Biomarkers in Addictive Disorders.
Biomolecules. 2021 Dec 3;11(12):1824. doi: 10.3390/biom11121824.
本文引用的文献
1
β-arrestin 2 regulates Toll-like receptor 4-mediated apoptotic signalling through glycogen synthase kinase-3β.
Immunology. 2010 Aug;130(4):556-63. doi: 10.1111/j.1365-2567.2010.03256.x. Epub 2010 May 20.
2
HIV-1 gp120 primes lymphocytes for opioid-induced, beta-arrestin 2-dependent apoptosis.
Biochim Biophys Acta. 2009 Aug;1793(8):1366-71. doi: 10.1016/j.bbamcr.2009.05.007. Epub 2009 May 27.
3
Chronic restraint stress promotes immune suppression through toll-like receptor 4-mediated phosphoinositide 3-kinase signaling.
J Neuroimmunol. 2008 Nov 15;204(1-2):13-9. doi: 10.1016/j.jneuroim.2008.08.011.
4
Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia.
Brain Behav Immun. 2008 Nov;22(8):1178-89. doi: 10.1016/j.bbi.2008.05.004. Epub 2008 Jul 2.
5
Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses.
J Neuroimmunol. 2008 Feb;194(1-2):70-82. doi: 10.1016/j.jneuroim.2007.11.018.
6
Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward.
ScientificWorldJournal. 2007 Nov 2;7:98-111. doi: 10.1100/tsw.2007.230.
7
Glial toll-like receptor signaling in central nervous system infection and autoimmunity.
Brain Behav Immun. 2008 Feb;22(2):140-7. doi: 10.1016/j.bbi.2007.08.011. Epub 2007 Oct 24.
8
Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits.
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13798-803. doi: 10.1073/pnas.0702553104. Epub 2007 Aug 10.
9
The beta2 adrenergic receptor regulates morphine tolerance and physical dependence.
Behav Brain Res. 2007 Jul 19;181(1):118-26. doi: 10.1016/j.bbr.2007.03.037. Epub 2007 Apr 7.
10
Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia.
J Neuroinflammation. 2007 Apr 30;4:11. doi: 10.1186/1742-2094-4-11.
Zotero 插件