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Naloxone Protects Rat Dopaminergic Neurons against Inflammatory Damage through Inhibition of Microglia Activation and Superoxide Generation
Abstract
Degeneration of dopaminergicrgic neurons in the substantia nigra of the brain is a hallmark of Parkinson's disease and inflammation and oxidative stress are closely associated with the pathogenesis of degenerative neurological disorders. Treatment of rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS)-activated microglia, resident immune cells of the brain, to release proinflammatory and neurotoxic factors tumor necrosis factor-alpha, interleukin-1beta, nitric oxide, and superoxide and subsequently caused damage to midbrain neurons, including dopaminergic neurons. The LPS-induced degeneration of the midbrain neurons was significantly reduced by cotreatment with naloxone, an opioid receptor antagonist. This study focused on understanding the mechanism of action for the protective effect of naloxone on dopaminergic neurons because of relevance to Parkinson's disease. Both naloxone and its opioid receptor inactive stereoisomer (+)-naloxone protected the dopaminergic neurons with equal potency. Naloxone inhibited LPS-induced activation of microglia and release of proinflammatory factors, and inhibition of microglia generation of superoxide free radical best correlated with the neuroprotective effect of naloxone isomers. To further delineate the site of action, naloxone was found to partially inhibit the binding of [(3)H]LPS to cell membranes, whereas it failed to prevent damage to dopaminergic neurons by peroxynitrite, a product of nitric oxide and superoxide. These results suggest that naloxone at least in part interferes with the binding of LPS to cell membranes to inhibit microglia activation and protect dopaminergic neurons as well as other neurons in the midbrain cultures from inflammatory damage.
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“Alternative drugs with anti-inflammatory properties, including dexamethasone, minocycline, naloxone, are going to be or have already been tested in preclinical and clinical trials.560–562”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [562]
Citations
Cites
Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
Green, L. C., Wagner, D. A., Glogowski, J. A., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982) · Analytical Biochemistry · doi:10.1016/0003-2697(82)90118-x · Cited by 12,061
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990
Phylogenetic Perspectives in Innate Immunity
Hoffmann, J. A., Kafatos, F. C., Janeway, C. A., & Ezekowitz, R. A. B. (1999) · Science · doi:10.1126/science.284.5418.1313 · Cited by 2,524
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · cited 1×
“It is well accepted that proinflammatory and cytotoxic factors produced by activated microglia contribute to neurodegeneration and that prevention of microglia activation serves to reduce neuronal injury (McGeer and McGeer, 1995; Epstein, 1998).”
Activated microglia mediate neuronal cell injury via a nitric oxide mechanism
Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., & Peterson, P. K. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.149.8.2736 · Cited by 1,138
Banati, R. B., Gehrmann, J., Schubert, P., & Kreutzberg, G. W. (1993) · Glia · doi:10.1002/glia.440070117 · Cited by 1,032
Oxidative stress and the pathogenesis of Parkinson's disease
Jenner, P., & Olanow, C. W. (1996) · Neurology · doi:10.1212/wnl.47.6_suppl_3.161s · Cited by 971
Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death
Boje, K. M., & Arora, P. K. (1992) · Brain Research · doi:10.1016/0006-8993(92)91004-x · Cited by 944
Beckman, J. S., Carson, M. A., Smith, C. D. L., & Koppenol, W. H. (1993) · Nature · doi:10.1038/364584a0 · Cited by 876
Cited by
Sorted by citations
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
“Naloxone has been shown to safeguard dopaminergic neurons by impeding microglial activation and the production of pro-inflammatory cytokines.(477) Similarly, celecoxib protects dopaminergic neurons from degeneration by suppressing microglial activation via inhibiting COX-2 in a rat model of PD.”
BackgroundLiu, B., & Hong, J.-S. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.035048 · Cited by 1,095
“First, neurodegeneration induced by a single bolus application of microgram levels of LPS occurred within a few days (Castano et al., 1998; Liu et al., 2000d; Lu et al., 2000; Iravani et al., 2002).”
BackgroundInfluentialSelf-citationNeuroinflammation in Parkinson's disease and its potential as therapeutic target
Wang, Q., Liu, Y., & Zhou, J. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0042-0 · Cited by 884
“The compound dramatically reverses the acute dystonia and parkinsonism following general anaesthesia [115, 116].”
BackgroundKim, W., Mohney, R. P., Wilson, B. C., Jeohn, G., Liu, B., & Hong, J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06309.2000 · Cited by 881
“Enriched microglia were prepared following a previously described protocol (Liu et al., 2000a).”
BackgroundMethodInfluentialSelf-citationWhy neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression
Gao, H., & Hong, J. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.05.002 · Cited by 852
Self-citationImamura, K., Hishikawa, N., Sawada, M., Nagatsu, T., Yoshida, M., & Hashizume, Y. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0766-2 · Cited by 791
“Many studies indicate the vulnerability of neurons to the potential toxicity of microglia that produce neurotoxic substances including superoxide anion, nitric oxide (NO), glutamate and pro-inflammatory cytokines [10, 11, 19, 26, 27, 30, 38].”
BackgroundInflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications
Pajares, M., I. Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020) · Cells · doi:10.3390/cells9071687 · Cited by 779
Role of Microglia in Central Nervous System Infections
Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., & Peterson, P. K. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.4.942-964.2004 · Cited by 723
“Preliminary data suggest that drugs such as minocycline (104, 352), naloxone (60, 206), dextromethorphan (209), and agents that up-regulate glutamate receptors (137, 349) have neuroprotective properties through their effects on microglial cells.”
BackgroundGao, H., Jiang, J., Wilson, B. C., Zhang, W., Hong, J., & Liu, B. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00928.x · Cited by 690
“…immunostaining, of the 24 sections covering a range of the nigral complex approximately 4.5–5.4 mm posterior to bregma (rostral to cordial) for each animal, 12 evenly spaced sections (i.e. every other one) were selected for visual counting of the number of nigral TH-IR neurons (Liu et al. 2000a).”
BackgroundMethodInfluentialSelf-citationTansey, M. G., McCoy, M. K., & Frank-Cannon, T. C. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.07.004 · Cited by 587
“Biochemical studies indicate HNE can covalently modify proteins, block mitochondrial respiration (Picklo et al., 1999), and induce caspase-dependent apoptosis (Liu et al., 2000b).”
BackgroundEvidence that opioids may have toll-like receptor 4 and MD-2 effects
Hutchinson, M. R., Zhang, Y., Shridhar, M., Evans, J. H., Buchanan, M. M., Zhao, T. X., Slivka, P. F., Coats, B. D., Rezvani, N., Wieseler, J. L., et al. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.08.004 · Cited by 575
“An alternative hypothesis of (+)isomer inhibition of a disparate enzyme has been postulated (Liu et al., 2000), but this line of evidence cannot explain the proinflammatory glial activation caused by opioid agonists, as it is unlikely opioid agonists cause activation of the enzyme postulated by Liu et al.”
InfluentialMPTP Mouse Models of Parkinson’s Disease: An Update
Meredith, G. E., & Rademacher, D. J. (2011) · Journal of Parkinson's Disease · doi:10.3233/jpd-2011-11023 · Cited by 471
“Importantly, MPP+ induces the opening of the mitochondrial transition pore through the inhibition of complex I and the production of ROS [38].”
BackgroundInfluentialDistinct Role for Microglia in Rotenone-Induced Degeneration of Dopaminergic Neurons
Gao, H., Hong, J., Zhang, W., & Liu, B. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00782.2002 · Cited by 439
Self-citationNeuroinflammation and Oxidation/Nitration of α-Synuclein Linked to Dopaminergic Neurodegeneration
Gao, H., Kotzbauer, P. T., Uryu, K., Leight, S., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0143-07.2008 · Cited by 450
“Moreover, suppressing neuroinflammation mitigates dopaminergic neurodegeneration in some of these animal models (Liu et al., 2000; Gao et al., 2003b; Choi et al., 2005).”
BackgroundRole of Nitric Oxide in Inflammation‐Mediated Neurodegeneration
Liu, B., Gao, H., Wang, J., Jeohn, G., Cooper, C. L., & Hong, J. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04077.x · Cited by 425
Self-citationHutchinson, M. R., Shavit, Y., Grace, P. M., Rice, K. C., Maier, S. F., & Watkins, L. R. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.004135 · Cited by 397
“…against NMDA- and quinolinate-induced neurotoxicity (Kim et al., 1987; Choi and Viseskul, 1988), blocking tritiated-LPS binding to microglia (Liu et al., 2000a,), and protecting dopamine neurons against LPS-induced neurotoxicity in vitro or in vivo by multiple actions, including decreasing…”
BackgroundNeuroinflammation, oxidative stress, and the pathogenesis of Parkinson’s disease
Mosley, R. L., Benner, E. J., Kadiu, I., Thomas, M., Boska, M. D., Hasan, K. M., Laurie, C. D., & Gendelman, H. E. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.09.006 · Cited by 393
“Inhibition of LPS binding to its cognate receptor inhibits activation of microglia, subsequent production and release of all proinflammatory factors and protection of dopaminergic neurons in culture [223].”
BackgroundBlock, M. L., Wu, X., Pei, Z., Li, G., Wang, T., Qin, L., Wilson, B. C., Yang, J. H., Hong, J., & Veronesi, B. (2004) · The FASEB Journal · doi:10.1096/fj.04-1945fje · Cited by 379
“Primary enriched microglia cultures were prepared from the whole brains of day-old Fisher 344 rat pups, using the procedure described previously (19).”
MethodSelf-citationHutchinson, M. R., Bland, S. T., Johnson, K. W., Rice, K. C., Maier, S. F., & Watkins, L. R. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.230 · Cited by 359
“Importantly, relating to our desired application, naloxone was documented to block microglial activation by LPS[29].”
BackgroundMethodInfluentialEarly Environmental Origins of Neurodegenerative Disease in Later Life
Landrigan, P. J., Sonawane, B., Butler, R. N., Trasande, L., Callan, R., & Droller, D. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7571 · Cited by 357
“In animal experiments, exposure to bacterial endotoxin lipopolysaccharide in utero induced dopaminergic neurodegeneration (Gao et al. 2002; Liu et al. 2000, 2003).”
BackgroundMcCoy, M. K., Martinez, T. N., Ruhn, K. A., Szymkowski, D. E., Smith, C. G., Botterman, B. R., Tansey, K. E., & Tansey, M. G. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1504-06.2006 · Cited by 370
“Primary rat ventral mesencephalic neuron/glia cultures were prepared by modification of a published protocol (Liu et al., 2000).”
MethodHe, Y., Appel, S. H., & Le, W. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02681-6 · Cited by 350
A possible role for humoral immunity in the pathogenesis of Parkinson's disease
Orr, C., Rowe, D. B., Mizuno, Y., Mori, H., & Halliday, G. M. (2005) · Brain · doi:10.1093/brain/awh625 · Cited by 365
“Direct inhibition of microglial activation (He et al., 2001; Liu et al., 2000; Wu et al., 2002) or therapeutic immunization using adoptive transfer of immune cells (Benner et al., 2004; Boska et al., 2005) is neuroprotective in these models.”
MethodCritical Role for Microglial NADPH Oxidase in Rotenone-Induced Degeneration of Dopaminergic Neurons
Gao, H., Liu, B., & Hong, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06181.2003 · Cited by 338
“Immunostaining was performed as described previously (Liu et al., 2000; Gao et al., 2003) with the following primary antibodies: anti-NeuN (1:2000; Chemicon, Temecula, CA), anti-F4/80 antigen (1:20; Serotec, Raleigh, NC), anti-GFAP (1:1000; Dako, Carpinteria, CA), and anti-TH (1:20,000; a gift from GlaxoSmithKline, Re…”
MethodSelf-citationNovel anti-inflammatory therapy for Parkinson's disease
Gao, H., Liu, B., Zhang, W., & Hong, J. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00176-7 · Cited by 325
Self-citationThe role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321
“Injectionwith the inflammogen LPS increases ethanol consumption in mice (Blednov et al., 2011).”
InfluentialInvolvement of Interferon-γ in Microglial-Mediated Loss of Dopaminergic Neurons
Mount, M. P., Lira, A., Grimes, D., Smith, P. D., Faucher, S., Slack, R. S., Anisman, H., Hayley, S. P., & Park, D. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.5321-06.2007 · Cited by 331
“5) mice, as described previously (Liu et al., 2000).”
An inflammatory review of Parkinson's disease
Orr, C. F., Rowe, D. B., & Halliday, G. M. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00127-2 · Cited by 309
Induction of innate immune genes in brain create the neurobiology of addiction
Crews, F. T., Zou, J., & Qin, L. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.03.003 · Cited by 313
“LPS, endotoxin, induces large innate immune responses that are blocked by opiate antagonists (Liu et al. 2000) and protect dopamine neurons through inhibition of microglial innate immune activation and reduced NOX formation of Brain Behav Immun.”
BackgroundInfluentialQin, L., Liu, Y., Cooper, C. L., Liu, B., Wilson, B. C., & Hong, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01210.x · Cited by 294
“Primary microglia were prepared from whole brains of 1-day Fisher 344 rat pups following a protocol described previously (Liu et al. 2000).”
MethodSelf-citationNeuroinflammation is a key player in Parkinson’s disease and a prime target for therapy
Li, Q., Flood, P. M., & Hong, J. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0428-1 · Cited by 295
“The neuroprotective potency of morphine is also similar to opioid receptor antagonist naloxone (Liu et al. 2000a, b).”
Self-citationLiu, B., Gao, H., & Hong, J. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.6361 · Cited by 285
“2001), and reactive oxygen species (ROS) such as superoxide anions (Gao et al. 2002a, 2002b; Liu et al. 2000a; Qin et al. 2002; Xie et al. 2002).”
BackgroundMethodInfluentialSelf-citationThe use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain
Younger, J., Parkitny, L., & McLain, D. (2014) · Clinical Rheumatology · doi:10.1007/s10067-014-2517-2 · Cited by 277
“in the brain and spinal cord is inhibited [23].”
BackgroundKim, S., Moon, M., & Park, S. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0132 · Cited by 263
“In fact, it has been demonstrated that several agents have neuroprotective effects due to their ability to suppress the microglial activation in several PD models (Liu et al. 2000, 2003, Wu et al. 2002, Delgado & Ganea 2003).”
Chen, P. S., Wang, C.-C., Bortner, C. D., Peng, G.-S., Wu, X., Pang, H., Lu, R.-B., Gean, P.-W., Chuang, D.-M., & Hong, J.-S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.06.053 · Cited by 262
“The release of TNF-α was measured with a rat TNF-α enzyme-linked immunosorbent assay kit (ELISA) from R&D System (Minneapolis, MN), and the production of nitric oxide (NO) was determined by measuring nitrite accumulations in the supernatant with Griess reagent, as described previously (Liu et al., 2000).”
MethodInfluentialSelf-citationMicroglia and neuroprotection: From in vitro studies to therapeutic applications
Polazzi, E., & Monti, B. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.06.009 · Cited by 269
Gao, H., Hong, J., Zhang, W., & Liu, B. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01228.2003 · Cited by 251
“Superoxide free radical, released by activated microglia through the multisubunit and membrane-bound NADPH oxidase, together with other microglia-originated factors, such as nitric oxide (NO), tumor necrosis factor- (TNF ), and interleukin-1- (IL-1 ), contribute significantly to dopaminergic neurodegeneration (Liu et…”
BackgroundMethodInfluentialSelf-citationRole of Cdk5-Mediated Phosphorylation of Prx2 in MPTP Toxicity and Parkinson's Disease
Qu, D., Rashidian, J., Mount, M. P., Aleyasin, H., Parsanejad, M., Lira, A., Haque, E., Zhang, Y., Callaghan, S. M., Daigle, M., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.033 · Cited by 257
“Alternatively, for midbrain neuronal cultures, the whole midbrain, without meninges and blood vessels, was collected from embryos aged 13.5 days gestation and processed as above and as similarly described (Liu et al., 2000).”
BackgroundMethodInfluentialIravani, M. M., Kashefi, K., Mander, P., Rose, S., & Jenner, P. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00562-0 · Cited by 247
Regulating Factors for Microglial Activation.
Nakamura, Y. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.945 · Cited by 241
Sánchez-Guajardo, V., Barnum, C. J., Tansey, M. G., & Romero‐Ramos, M. (2013) · ASN NEURO · doi:10.1042/an20120066 · Cited by 245
“Anti-inflammatory compounds, such as naloxane, minocycline and dexamethasone can reduce microglia activation and neuronal damage in different models of nigral degeneration (Liu et al., 2000; Lu et al., 2000; Tikka et al., 2001; Castano et al., 2002; Wu et al., 2002).”
BackgroundThe lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Dutta, G., Zhang, P., & Liu, B. (2008) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00616.x · Cited by 235
Self-citationFerrari, C. C., Pott Godoy, M. C., Tarelli, R., Chertoff, M., Depino, A. M., & Pitossi, F. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.06.013 · Cited by 235
“…addition, several anti-inflammatory agents such as minocycline and naloxone that have been shown to ameliorate neurodegeneration in PD models also diminished IL-1β expression in those models (reviewed in Hald and Lotharius, 2005; Liu et al., 2000a,b; Sanchez-Pernaute et al., 2004; Wu et al., 2002).”
BackgroundReciprocal Interactions Between Microglia and Neurons: From Survival to Neuropathology
Polazzi, E., & Contestabile, A. (2002) · Reviews in the Neurosciences · doi:10.1515/revneuro.2002.13.3.221 · Cited by 234
Role of reactive oxygen species in LPS‐induced production of prostaglandin E2in microglia
Wang, T., Qin, L., Liu, B., Liu, Y., Wilson, B. C., Eling, T. E., Langenbach, R. I., Taniura, S., & Hong, J. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02242.x · Cited by 220
Self-citationWang, M., Lin, W., Chen, H.-L., Chang, Y., Ou, H., Kuo, J., Hong, J., & Jeng, K.-C. G. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02290.x · Cited by 213
“The release of superoxide was determined by measuring the inhibition of reduction of cytochrome c by superoxide dismutase (SOD) as described previously (Liu et al., 2000).”
BackgroundMethodInfluentialSelf-citationFibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study
Younger, J., & Mackey, S. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00613.x · Cited by 216
“More recently, naltrexone (and its shorter acting cousin, naloxone) has also been found to attenuate the production of proinflammatory cytokines and neurotoxic superoxides via suppressive effects on central nervous system microglia cells [23–27].”
BackgroundQin, L., Li, G., Qian, X., Liu, Y., Wu, X., Liu, B., Hong, J., & Block, M. L. (2005) · Glia · doi:10.1002/glia.20225 · Cited by 218
“Primary enriched microglia cultures were prepared from the whole brains of two-day-old rat or mouse pups, using the previously described procedure (Liu et al., 2000).”
MethodSelf-citationYounger, J., Noor, N., McCue, R., & Mackey, S. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37734 · Cited by 209
Liu, Y., Qin, L., Li, G., Zhang, W., An, L., Liu, B., & Hong, J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043166 · Cited by 205
“The neuroprotective effect of naloxone has been observed in both the in vitro and in vivo models of inflammation-mediated neurodegeneration (Lu et al., 2000; Liu et al., 2000a,b, 2002b).”
BackgroundInfluentialSelf-citationZhang, W., Wang, T., Qin, L., Gao, H., Wilson, B. C., Ali, S. F., Zhang, W., Hong, J., & Liu, B. (2004) · The FASEB Journal · doi:10.1096/fj.03-0983fje · Cited by 206
“Primary mesencephalic neuron-glia cultures were prepared from the brains of embryonic day 12/13 C57BL/6J mice (Jackson Laboratory), following our previously described protocol (30) with subsequent modifications (31).”
MethodSelf-citationMoon, M., Kim, H. G., Hwang, L., Seo, J.-H., Kim, S., Hwang, S., Kim, S., Lee, D., Chung, H., Oh, M. S., et al. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9037-x · Cited by 203
“In fact, several agents have been found to be neuroprotective due to their ability to suppress the activation of microglia in various PD models (Liu et al. 2000; Wu et al. 2002; Breidert et al. 2002; Delgado and Ganea 2003; Liu et al. 2003).”
BackgroundTomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203
de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-34 · Cited by 201
“The neurotoxic effect of LPS has been also observed in mesencephalic cell cultures [30-33].”
BackgroundGayle, D. A., Ling, Z., Tong, C. W., Landers, T. M., Lipton, J. W., & Carvey, P. M. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(01)00315-7 · Cited by 201
Lipopolysaccharide Animal Models for Parkinson's Disease
Liu, M., & Bing, G. (2011) · Parkinson s Disease · doi:10.4061/2011/327089 · Cited by 199
“For example, naloxone, an antagonist of opioid receptors, provided the dopaminergic neuroprotective e ff ects against LPS damage [32, 38, 53].”
Arimoto, T., & Bing, G. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(02)00017-7 · Cited by 202
“Recently, a number of studies have shown that injection of LPS into the SN induced a selective dopaminergic neuronal loss (Castano et al., 1998; Herrera et al., 2000; Liu et al., 2000).”
BackgroundZhang, F., Shi, J., Zhou, H., Wilson, B. C., Hong, J., & Gao, H. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.064535 · Cited by 190
“Using in vitro midbrain neuron-glia cocultures, we have demonstrated a critical role of proinflammatory factor release from activated microglia in DA neurotoxicity (Liu et al., 2000).”
BackgroundMethodInfluentialSelf-citationHa, S. K., Lee, P., Park, J. A., Oh, H. R., Lee, S., Park, J. H., Lee, E. H., Ryu, J. H., Lee, K. R., & Kim, S. Y. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.10.005 · Cited by 187
“Naloxone reduces the neurotoxicity mediated by cytotoxic agents released from microglia in vitro and in vivo experiment (Liu et al., 2000a,b).”
BackgroundColler, J. K., & Hutchinson, M. R. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.01.008 · Cited by 186
“This TLR4 activity of (+)-naloxone (Hutchinson et al., 2008c) extends to the classical ligands of TLR4 with LPS-induced glial activation also blocked by (+)- naloxone (Liu et al., 2000b).”
BackgroundPeng, G.-S., Li, G., Tzeng, N., Chen, P.-S., Chuang, D., Hsu, Y., Yang, S., & Hong, J. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.10.021 · Cited by 169
Self-citationHaslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169
Liu, B., Jiang, J., Wilson, B. C., Du, L., Yang, S., Wang, J., Wu, G.-C., Cao, X.-D., & Hong, J. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38877-9 · Cited by 167
“Using rat mesencephalic neuron-glia cultures, we have recently demonstrated that treatment of the cultures with the bacterial endotoxin LPS induced the activation of microglia that in turn produced large quantities of TNFa, IL-1b, NO, and superoxide free radicals (Liu et al., 2000).”
InfluentialSelf-citationGene–environment interactions: Key to unraveling the mystery of Parkinson's disease
Gao, H., & Hong, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.03.005 · Cited by 166
Self-citationSayyah, M., Javadpour, M., & Ghazi‐Khansari, M. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.043 · Cited by 164
“001 compared with LPS (1 mg/kg) group. lus, which activates microglia to release the inflammatory mediators (Hetier et al., 1990; Lee et al., 1993; Liu et al., 2000a,b; Matoth et al., 2000; Turrin et al., 2001; Schuligoi et al., 2003).”
InfluentialThe Role of Microglia in Paraquat-Induced Dopaminergic Neurotoxicity
Wu, X.-F., Block, M. L., Zhang, W., Qin, L., Wilson, B. C., Zhang, W.-Q., Veronesi, B., & Hong, J. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.654 · Cited by 161
“2 demonstrates that only DA uptake was reduced significantly ( p < 0.01) by the addition of PQ to neuron-glia cultures, whereas GABA uptake remained unaffected ( p > 0.05).”
InfluentialSelf-citationRole of Endogenous Lipopolysaccharides in Neurological Disorders
Kalyan, M., Hediyal, T. A., Sonali, S., Vichitra, C., Sunanda, T., Praveenraj, S. S., Ray, B., Gorantla, V. R., Rungratanawanich, W., Mahalakshmi, A. M., et al. (2022) · Cells · doi:10.3390/cells11244038 · Cited by 170
“It causes microglial activation and the release of proinflammatory cytokines and neurotoxic factors such as IL-1β, TNF-α, prostaglandins, superoxide, and NO that damage dopaminergic neurons [49] via mitochondrial dysfunction and apoptosis [85,86].”
BackgroundLi, Q., Xu, Z., Zhang, W., Wilson, B. C., Hong, J., & Flood, P. M. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-23 · Cited by 153
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13– 14 mice, as described previously [18].”
BackgroundMethodResultInfluentialSelf-citationNeuroprotective effect of nicotine on dopaminergic neurons by anti‐inflammatory action
Park, H., Lee, P., Ahn, Y.-W., Choi, Y.-J., Lee, G., Lee, D.-Y., Chung, E., & Jin, B. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05636.x · Cited by 145
Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair
Siebert, J. R., Conta, A. C., & Osterhout, D. J. (2014) · BioMed Research International · doi:10.1155/2014/845323 · Cited by 158
“These experiments revealed a significant increase in microglia activation throughout this subcortical area preceding marked neuronal death [59].”
BackgroundEvidence of Inflammatory System Involvement in Parkinson’s Disease
Chao, Y., Wong, S. C., & Tan, E. K. (2014) · BioMed Research International · doi:10.1155/2014/308654 · Cited by 152
Chen, H.-Q., Jin, Z., Wang, X., Xu, X., Deng, L., & Zhao, J.-W. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.10.046 · Cited by 150
“Rat microglia-enriched cultures were prepared from whole brains of one-day-old Sprague-Dawley rats as described previously [9].”
InfluentialArimoto, T., Choi, D., Lü, X., Liu, M., Nguyen, X. V., Zheng, N., Stewart, C. A., Kim, H., & Bing, G. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.04.011 · Cited by 149
Awareness and current knowledge of Parkinson’s disease: a neurodegenerative disorder
Khan, A. U., Akram, M., Daniyal, M., & Zainab, R. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1486837 · Cited by 151
“Independent determinants for the progression of apathy include memory loss at baseline, axial impairment and a more quick decline in speech [245].”
BackgroundPatten, D. K., Schultz, B. G., & Berlau, D. J. (2018) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2086 · Cited by 136
“One rat study demonstrated that only a small dose of naloxone is needed to impact some of the functions of glial cells and macrophages.(14) A different in vitro study suggests that this may also be the case with naltrexone, although more weakly than naloxone.”
BackgroundMolecular consequences of activated microglia in the brain: overactivation induces apoptosis
Liu, B., Wang, K., Gao, H.-M., Mandavilli, B., Wang, J.-Y., & Hong, J.-S. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.t01-1-00216.x · Cited by 286
Self-citationLi, F.-Q., Wang, T., Pei, Z., Liu, B., & Hong, J. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0213-0 · Cited by 135
Self-citationTian, Y.-Y., An, L., Jiang, L., Duan, Y.-L., Chen, J., & Jiang, B. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.09.010 · Cited by 132
“Injection of bacterial lipopolysaccharide (LPS) into rat SN and the ensuing microglial activation has been shown to induce dopaminergic neurodegeneration (Liu et al., 2000b; Iravani et al., 2002).”
MethodWang, T., Liu, B., Zhang, W., Wilson, B. C., & Hong, J. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.059683 · Cited by 133
“Reagents.”
BackgroundMethodInfluentialSelf-citationImamura, K., Hishikawa, N., Ono, K., Suzuki, H., Sawada, M., Nagatsu, T., Yoshida, M., & Hashizume, Y. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0919-y · Cited by 133
“Many studies indicate the vulnerability of neurons to the potential toxicity of microglia, which produces neurotoxic substances including superoxide anion, nitric oxide (NO), glutamate, and pro-inflammatory cytokines [8, 9, 22, 23, 26, 35, 37, 40, 47].”
BackgroundLi, Q., Wei, S., Zhang, D., Hu, X., Xu, Z., Wilson, B. C., Benna, J. E., Hong, J., & Flood, P. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.660 · Cited by 130
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13–14 mice, as described previously (31, 32).”
MethodSelf-citationFluoxetine protects neurons against microglial activation-mediated neurotoxicity
Zhang, F., Zhou, H., Wilson, B. C., Shi, J.-S., Hong, J.-S., & Gao, H.-M. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70066-9 · Cited by 123
“Rat primary neuron-glia, neuron-astrocyte, neuron-microglia and neuron-enriched cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats as described previously [10, 11].”
MethodSelf-citationCurrent and Emerging Pharmacotherapy for Fibromyalgia
Tzadok, R., & Ablin, J. N. (2020) · Pain Research and Management · doi:10.1155/2020/6541798 · Cited by 122
“Inhibition of microglial activation by naltrexone or naloxone therefore has an anti-inflammatory effect through the decrease in production of neurotoxic chemicals [66, 67], which is suggested to contribute to its analgesic effect [25].”
BackgroundSelley, M. L. (2005) · Brain Research · doi:10.1016/j.brainres.2004.02.083 · Cited by 122
Arai, H., Furuya, T., Yasuda, T., Miura, M., Mizuno, Y., & Mochizuki, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407328200 · Cited by 122
Li, Q., Wu, H., Chen, S., Zhang, D., Ali, S. F., Peterson, L. J., Wilson, B. C., Lu, R., Hong, J., & Flood, P. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002449 · Cited by 118
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13–14 mice, as described previously (21, 22).”
MethodSelf-citationUpdates on immunity and inflammation in Parkinson disease pathology
Joshi, N., & Singh, S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24185 · Cited by 118
Wang, S., Hu, L., Gao, X., Guo, H. W., & Fan, G. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0151-1 · Cited by 117
Shih, Y.-T., Chen, P. S., Wu, C.-H., Tseng, Y.-T., Wu, Y., & Lo, Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.07.017 · Cited by 116
“Primary cortical neuron cultureswere prepared from gestation day 15–16 rat embryos and cultured as described previously [39].”
MethodTomás‐Camardiel, M., Venero, J. L., Herrera, A. J., de Pablos, R. M., Pintor‐Toro, J. A., Machado, A., & Cano, J. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20443 · Cited by 116
“Statistical significance (Student’s t-test): *P < 0.05; **P < 0.01 comparing the E2-treated and untreated animals for every time point. death of dopaminergic neurons (Castaño et al., 1998; Liu et al., 2000; Lu et al., 2000; Gao et al., 2002).”
BackgroundInfluentialMicroglial regulation of immunological and neuroprotective functions of astroglia
Chen, S., Oyarzabal, E. A., Sung, Y.-F., Chu, C., Wang, Q., Chen, S.-L., Lu, R., & Hong, J.-S. (2014) · Glia · doi:10.1002/glia.22738 · Cited by 115
“NO was assessed by measuring nitrite in 50 mL of supernatants using Griess reagent as described previously (Liu et al., 2000).”
MethodSelf-citationMcCoy, M. K., Ruhn, K. A., Martinez, T. N., McAlpine, F. E., Blesch, A., & Tansey, M. G. (2008) · Molecular Therapy · doi:10.1038/mt.2008.146 · Cited by 121
Li, Q., Block, M. L., Wei, S., Lin, C., Reece, J. M., Pang, H., Wilson, B. C., Hong, J., & Flood, P. M. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.106351 · Cited by 110
Self-citationNeuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation
Wang, S., Wang, H., Guo, H. W., Kang, L., Gao, X., & Hu, L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.04.005 · Cited by 107
Pei, Z., Pang, H., Qian, L., Yang, S., Wang, T., Zhang, W., Wu, X., Dallas, S., Wilson, B., Reece, J. M., et al. (2007) · Glia · doi:10.1002/glia.20545 · Cited by 105
“Primary enriched microglia cultures were prepared from the whole brains of day-old mouse pups (MAC1, MAC1, TLR4, TLR4, PHOX, and PHOX) using the procedure described previously (Liu et al., 2000).”
MethodSelf-citationIn vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS
Polikov, V. S., Block, M. L., Fellous, J., Hong, J., & Reichert, W. M. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.06.018 · Cited by 107
Self-citationJeong, H., Jou, I., & Joe, E.-H. (2010) · Experimental & Molecular Medicine · doi:10.3858/emm.2010.42.12.085 · Cited by 104
“Cultured microglia challenged with LPS and interferon-γ produce neurotoxic inflammatory mediators including inducible nitric oxide synthase (iNOS) (Liu et al., 2000; Possel et al., 2000; Min et al., 2006), whereas microglia activated in vivo by brain injury and/or LPS injection synthesize very…”
Herrera, A. J., Tomás‐Camardiel, M., Venero, J. L., Cano, J., & Machado, A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0121-3 · Cited by 103
“These and other microglial factors could contribute significantly to dopaminergic degeneration (Liu et al., 2000; Gao et al., 2002).”
Mathieu, P., Battista, D., Depino, A. M., Roca, V., Graciarena, M., & Pitossi, F. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06548.x · Cited by 112
“…the substantia nigra are particularly susceptible to microglial-mediated toxicity in vitro and in vivo (Castano et al. 1998, 2002; Kim et al. 2000; Liu et al. 2000) and this effect could be reversed by the administration of anti-inflammatory drugs (Liu et al. 2000; Castano et al. 2002;…”
Background
Metadata
- Authors
- Liu, B., Du, L., & Hong, J.-S.
- Affiliations
- National Institutes of Health (US)
- National Institute of Environmental Health Sciences (US)
- Corresponding author
- Liu, Bin
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 293
- Issue
- 2
- Pages
- 607-617
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1891696008
- Cited by
- 347
- References
- 43
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 12 · 2016: 10 · 2015: 16 · 2014: 11 · 2013: 13 · 2012: 26
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- naloxone, dopaminergic neurons, Parkinson's disease, microglial activation, lipopolysaccharide, neuroinflammation, oxidative stress, superoxide, neuroprotection, substantia nigra, opioid antagonists, peroxynitrite, nitric oxide, inflammatory cytokines
- MeSH terms
- Animals, Cells, Cultured, Dopamine, Immunohistochemistry, Inflammation, Interleukin-1, Lipopolysaccharides, Mesencephalon, Naloxone, Narcotic Antagonists, Neurons, Nitrates, Nitrites, Rats, Inbred F344, Stereoisomerism, Substantia Nigra, Superoxides, Tumor Necrosis Factor-alpha, Tyrosine 3-Monooxygenase, Oxidants, Microglia, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Rats
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