18kDa 转位蛋白配体对喹啉酸注射大鼠纹状体中小胶质细胞激活和神经元死亡的影响。
Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum.
机构信息
Department of Pharmacology, Bosch Institute and School of Medical Sciences, University of Sydney, NSW 2006, Australia.
出版信息
ACS Chem Neurosci. 2012 Feb 15;3(2):114-9. doi: 10.1021/cn200099e. Epub 2011 Dec 12.
Abstract
There is evidence that excitotoxicity and prolonged microglial activation are involved in neuronal death in neurodegenerative disorders. Activated microglia express various molecules, including the translocator protein 18 kDa (TSPO; formerly known as the peripheral benzodiazepine receptor) on the outer mitochondrial membrane. The TSPO is a novel target for neuroprotective treatments which aim to reduce microglial activation. The effect of PK 11195 and three other TSPO ligands on the level of microglial activation and neuronal survival was evaluated in a quinolinic acid (QUIN) rat model of excitotoxic neurodegeneration. All three ligands were neuroprotective at a level comparable to PK 11195. All of the ligands decreased microglial activation following the injection of QUIN but had no effect on astrogliosis. Interestingly, we also observed neuroprotective effects from the vehicle, dimethyl sulfoxide (DMSO).
摘要
有证据表明，兴奋性毒性和持续的小胶质细胞激活参与了神经退行性疾病中的神经元死亡。活化的小胶质细胞在外膜上表达各种分子，包括 18 kDa 转位蛋白（TSPO；以前称为外周苯二氮䓬受体）。TSPO 是神经保护治疗的新靶点，旨在减少小胶质细胞激活。在喹啉酸（QUIN）兴奋性神经退行性变大鼠模型中，评估了 PK 11195 和其他三种 TSPO 配体对小胶质细胞激活和神经元存活水平的影响。所有三种配体的神经保护作用与 PK 11195 相当。所有配体在注射 QUIN 后均降低了小胶质细胞的激活，但对星形胶质细胞增生没有影响。有趣的是，我们还观察到载体二甲基亚砜（DMSO）的神经保护作用。
相似文献
1
Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum.
ACS Chem Neurosci. 2012 Feb 15;3(2):114-9. doi: 10.1021/cn200099e. Epub 2011 Dec 12.
2
Peripheral benzodiazepine receptor ligand PK11195 reduces microglial activation and neuronal death in quinolinic acid-injected rat striatum.
Neurobiol Dis. 2005 Nov;20(2):550-61. doi: 10.1016/j.nbd.2005.04.010.
3
4
Translocator protein 18 kDa is involved in the regulation of reactive gliosis.
Glia. 2007 Nov 1;55(14):1426-36. doi: 10.1002/glia.20558.
5
Microglial expression of prostaglandin EP3 receptor in excitotoxic lesions in the rat striatum.
Neurochem Int. 2004 Oct;45(5):653-60. doi: 10.1016/j.neuint.2004.04.007.
6
VEGF receptor antagonist Cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult.
J Neuroinflammation. 2008 May 20;5:18. doi: 10.1186/1742-2094-5-18.
7
Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity.
J Neuroinflammation. 2023 Feb 13;20(1):34. doi: 10.1186/s12974-023-02714-z.
8
Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation.
Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2203-11. doi: 10.1007/s00259-008-0834-x. Epub 2008 Jun 7.
9
Neuroprotective effect of Ro5-4864 following brain injury.
Exp Neurol. 2008 Dec;214(2):201-8. doi: 10.1016/j.expneurol.2008.08.008. Epub 2008 Aug 27.
10
Translocator protein (18 kDa)/peripheral benzodiazepine receptor specific ligands induce microglia functions consistent with an activated state.
Glia. 2011 Feb;59(2):219-30. doi: 10.1002/glia.21091.
引用本文的文献
1
GRT-X Stimulates Dorsal Root Ganglia Axonal Growth in Culture via TSPO and Kv7.2/3 Potassium Channel Activation.
Int J Mol Sci. 2024 Jul 3;25(13):7327. doi: 10.3390/ijms25137327.
2
Translocator protein in the rise and fall of central nervous system neurons.
Front Cell Neurosci. 2023 Jun 21;17:1210205. doi: 10.3389/fncel.2023.1210205. eCollection 2023.
3
Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration.
ACS Chem Neurosci. 2022 Nov 16;13(22):3188-3197. doi: 10.1021/acschemneuro.2c00582. Epub 2022 Oct 27.
4
TSPO imaging in animal models of brain diseases.
Eur J Nucl Med Mol Imaging. 2021 Dec;49(1):77-109. doi: 10.1007/s00259-021-05379-z. Epub 2021 Jul 10.
5
The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):831-846. doi: 10.1080/14756366.2021.1900158.
6
The Protective Effect of PK-11195 on Cognitive Impairment in Rats Survived of Polymicrobial Sepsis.
Mol Neurobiol. 2021 Jun;58(6):2724-2733. doi: 10.1007/s12035-021-02294-0. Epub 2021 Jan 25.
7
Translation Imaging in Parkinson's Disease: Focus on Neuroinflammation.
Front Aging Neurosci. 2020 Jun 5;12:152. doi: 10.3389/fnagi.2020.00152. eCollection 2020.
8
The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes.
Cells. 2020 Feb 24;9(2):512. doi: 10.3390/cells9020512.
9
Microglial Pro-Inflammatory and Anti-Inflammatory Phenotypes Are Modulated by Translocator Protein Activation.
Int J Mol Sci. 2019 Sep 10;20(18):4467. doi: 10.3390/ijms20184467.
10
The TSPO Ligands 2-Cl-MGV-1, MGV-1, and PK11195 Differentially Suppress the Inflammatory Response of BV-2 Microglial Cell to LPS.
Int J Mol Sci. 2019 Jan 30;20(3):594. doi: 10.3390/ijms20030594.
本文引用的文献
1
Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO).
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5799-802. doi: 10.1016/j.bmcl.2010.07.135. Epub 2010 Aug 4.
2
Learning impairment caused by intra-CA1 microinjection of testosterone increases the number of astrocytes.
Behav Brain Res. 2010 Mar 17;208(1):30-7. doi: 10.1016/j.bbr.2009.11.004. Epub 2009 Nov 10.
3
Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography.
Curr Med Chem. 2009;16(22):2899-923. doi: 10.2174/092986709788803150.
4
Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans.
J Nucl Med. 2009 Aug;50(8):1276-82. doi: 10.2967/jnumed.109.062265. Epub 2009 Jul 17.
5
[11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis.
Mol Imaging Biol. 2009 Nov-Dec;11(6):386-98. doi: 10.1007/s11307-009-0211-6. Epub 2009 Mar 28.
6
Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation.
J Nucl Med. 2009 Mar;50(3):468-76. doi: 10.2967/jnumed.108.058669. Epub 2009 Feb 17.
7
The translocator protein (18 kDa): central nervous system disease and drug design.
J Med Chem. 2009 Feb 12;52(3):581-92. doi: 10.1021/jm8011678.
8
Neuroprotective effects of a selective N-methyl-D-aspartate NR2B receptor antagonist in the 6-hydroxydopamine rat model of Parkinson's disease.
Clin Exp Pharmacol Physiol. 2008 Nov;35(11):1388-94. doi: 10.1111/j.1440-1681.2008.05046.x.
9
11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation.
J Nucl Med. 2007 Apr;48(4):573-81. doi: 10.2967/jnumed.106.036764.
10
Microglial activation correlates with severity in Huntington disease: a clinical and PET study.
Neurology. 2006 Jun 13;66(11):1638-43. doi: 10.1212/01.wnl.0000222734.56412.17.
Zotero 插件