Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia
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Adult exposure to NMDA receptor antagonists, such as ketamine, produces psychosis in humans, and exacerbates symptoms in schizophrenic patients. We recently showed that ketamine activates the innate immune enzyme NADPH-oxidase in brain, and that the superoxide produced leads to dysfunction of a subset of fast-spiking inhibitory interneurons expressing the calcium-binding protein parvalbumin (PV). Here we show that neuronal production of interleukin-6 (IL-6) is necessary and sufficient for ketamine-mediated activation of NADPH-oxidase in brain. Removal of IL-6 in neuronal cultures by anti-IL-6 blocking antibodies, or in vivo by use of IL-6-deficient mice, prevented the increase in superoxide by ketamine and rescued the interneurons. Accumulating evidence suggests that schizophrenia patients suffer from diminished antioxidant defenses, and a recent clinical trial showed that enhancing these defenses may ameliorate symptoms of the disease. Our results showing that ketamine-induced IL-6 is responsible for the activation of NADPH-oxidase in brain suggest that reducing brain levels of this cytokine may protect the GABAergic phenotype of fast-spiking PV-interneurons and thus attenuate the propsychotic effects of ketamine.
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Ketamine, a pro-inflammatory stimulus, injures PV-INs in vitro and in vivo.
“For example, the NMDA receptor antagonist ketamine, a pro-inflammatory stimulus, injures PV-INs in vitro and in vivo [16,95].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [95]
This PV-IN injury is linked to IL-6-mediated, Nox2-dependent NADPH oxidase activation and superoxide production.
“This injury is connected to IL-6mediated Nox2-dependent NADPH oxidase activation and production of superoxide [16,95].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [95]
Noncompeting NMDA antagonists affect inhibitory interneuron function by altering redox mechanisms, an effect that depends on interleukin 6 and other cytokines.
“Noncompeting NMDA antagonists affect inhibitory interneuron function by altering redox mechanisms, 74 an effect that depends on interleukin 6 and other cytokines.75”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [75]
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Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · see citing works
Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · see citing works
Jentsch, J., & Roth, R. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00060-8 · Cited by 1,349 · see citing works
Homayoun, H., & Moghaddam, B. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2213-07.2007 · Cited by 1,231 · see citing works
Kawasaki, Y., Zhang, L., Cheng, J.-K., & Ji, R.-R. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3338-07.2008 · Cited by 1,162 · see citing works
NMDA receptor hypofunction model of schizophrenia
Olney, J. W., Newcomer, J. W., & Farber, N. B. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(99)00029-1 · Cited by 1,020 · see citing works
Akbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002 · see citing works
Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06315.2003 · Cited by 938 · see citing works
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Behrens, M. M., Ali, S. S., Dao, D. N., Lucero, J., Shekhtman, G., Quick, K. L., & Dugan, L. L. (2007) · Science · doi:10.1126/science.1148045 · Cited by 585 · see citing works
Self-citationJavitt, D. C. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(06)78003-5 · Cited by 563 · see citing works
Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., Judd, F., Katz, F., Katz, P., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.004 · Cited by 552 · see citing works
Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
Do, K. Q., Trabesinger, A. H., Kirsten‐Krüger, M., Lauer, C. J., Dydak, U., Hell, D., Holsboer, F., Boesiger, P., & Cuénod, M. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00229.x · Cited by 540 · see citing works
Prenatal Infection as a Risk Factor for Schizophrenia
Brown, A. S. (2006) · Schizophrenia Bulletin · doi:10.1093/schbul/sbj052 · Cited by 540 · see citing works
Interleukin-6 (IL-6)—A molecule with both beneficial and destructive potentials
Gadient, R. A., & Otten, U. (1997) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00021-x · Cited by 481 · see citing works
Meyer, U., Nyffeler, M., Yee, B. K., Knuesel, I., & Feldon, J. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.09.012 · Cited by 457 · see citing works
Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics
BEASLEY, C., & REYNOLDS, G. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(96)00122-3 · Cited by 426 · see citing works
Byrne, J., Grieve, D., Bendall, J. K., Li, J., Gove, C. D., Lambeth, J. D., Cave, A. C., & Shah, A. M. (2003) · Circulation Research · doi:10.1161/01.res.0000099504.30207.f5 · Cited by 411 · see citing works
Cysteine regulation of protein function – as exemplified by NMDA-receptor modulation
Lipton, S. A., Choi, Y.-B., Takahashi, H., Zhang, D., Li, W., Godzik, A., & Bankston, L. A. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02245-2 · Cited by 375 · see citing works
Kinney, J. W., Davis, C. N., Tabarean, I., Conti, B., Bartfai, T., & Behrens, M. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4722-05.2006 · Cited by 329 · see citing works
Self-citationChattopadhyaya, B., Cristo, G. D., Wu, C. Z., Knott, G. W., Kuhlman, S. J., Fu, Y., Palmiter, R. D., & Huang, Z. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.015 · Cited by 326 · see citing works
Altered glutathione redox state in schizophrenia.
Yao, J. K., Leonard, S., & Reddy, R. (2006) · Disease Markers · doi:10.1155/2006/248387 · Cited by 321 · see citing works
A Review of the Fetal Brain Cytokine Imbalance Hypothesis of Schizophrenia
Meyer, U., Feldon, J., & Yee, B. K. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn022 · Cited by 318 · see citing works
Interleukin‐6: a cytokine to forget
Balschun, D., Wetzel, W., del Rey, A., Pitossi, F. J., Schneider, H., Zuschratter, W., & Besedovsky, H. O. (2004) · The FASEB Journal · doi:10.1096/fj.04-1625fje · Cited by 317 · see citing works
Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence
Gysin, R., Kraftsik, R., Sandell, J., Bovet, P., Chappuis, C., Conus, P., Deppen, P., Preisig, M., Ruiz, V., Steullet, P., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706778104 · Cited by 309 · see citing works
Sparkman, N. L., Buchanan, J. B., Heyen, J. R. R., Chen, J., Beverly, J. L., & Johnson, R. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3376-06.2006 · Cited by 307 · see citing works
NMDA receptor channels: Subunit-specific potentiation by reducing agents
Köhr, G., Eckardt, S., Lüddens, H., Monyer, H., & Seeburg, P. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90311-5 · Cited by 255 · see citing works
Rujescu, D., Bender, A., Keck, M. E., Hartmann, A. M., Ohl, F., Ræder, H., Giegling, I., Genius, J., McCarley, R. W., Möller, H., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.029 · Cited by 239 · see citing works
Cochran, S. M., Kennedy, M., McKerchar, C. E., Steward, L. J., Pratt, J. A., & MORRIS, B. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300031 · Cited by 236 · see citing works
Schizophrenia and Oxidative Stress: Glutamate Cysteine Ligase Modifier as a Susceptibility Gene
Tosic, M., Ott, J., Barral, S., Bovet, P., Deppen, P., Gheorghita, F., Matthey, M.-L., Parnas, J., Preisig, M., Saraga, M., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/507566 · Cited by 234 · see citing works
Keilhoff, G., Becker, A., Grecksch, G., Wolf, G. L., & Bernstein, H. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.039 · Cited by 200 · see citing works
A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice
Quick, K. L., Ali, S. S., Arch, R. H., Xiong, C., Wozniak, D. F., & Dugan, L. L. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.09.014 · Cited by 184 · see citing works
Self-citationSamland, H., Huitrón‐Reséndiz, S., Masliah, E., Criado, J. R., Henriksen, S. J., & Campbell, I. L. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10635 · Cited by 178 · see citing works
Wang, C. Z., Yang, S. F., Xia, Y., & Johnson, K. M. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301647 · Cited by 161 · see citing works
The effects of maternal inflammation on neuronal development: possible mechanisms
Jonakait, G. M. (2007) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2007.08.017 · Cited by 141 · see citing works
Mustafa, A. K., Kumar, M., Selvakumar, B., Ho, G. P. H., Ehmsen, J. T., Barrow, R. K., Amzel, L. M., & Snyder, S. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611620104 · Cited by 136 · see citing works
Induction of Interleukin-6 by Depolarization of Neurons
Sallmann, S., Jüttler, E., Prinz, S., Petersen, N., Knopf, U., Weiser, T., & Schwaninger, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-23-08637.2000 · Cited by 122 · see citing works
D’Arcangelo, G., Tancredi, V., Onofri, F., D’Antuono, M., Giovedı̀, S., & Benfenati, F. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00011.x · Cited by 117 · see citing works
Holcomb, H. H., Lahti, A. C., Medoff, D. R., Cullen, T. J., & Tamminga, C. A. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300824 · Cited by 108 · see citing works
Zhang, Y., Behrens, M. M., & Lisman, J. E. (2008) · Journal of Neurophysiology · doi:10.1152/jn.00079.2008 · Cited by 107 · see citing works
Self-citationCochran, S. M., Fujimura, M., MORRIS, B. J., & Pratt, J. A. (2002) · Synapse · doi:10.1002/syn.10126 · Cited by 85 · see citing works
Cabungcal, J.-H., Preissmann, D., Delseth, C., Cuénod, M., Kim, Q., & Schenk, F. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.03.001 · Cited by 83 · see citing works
The Risk for Schizophrenia From Childhood and Adult Infections
Brown, A. S. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07101637 · Cited by 80 · see citing works
Volterra, A., Trotti, D., FLORIDI, S., & Racagni, G. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb21800.x · Cited by 73 · see citing works
Tomitaka, S., Tomitaka, M., Tolliver, B. K., & Sharp, F. R. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00018.x · Cited by 69 · see citing works
Xi, D., Keeler, B. E., Zhang, W., Houlé, J. D., & Gao, W. (2008) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.09.013 · Cited by 66 · see citing works
Zuo, D., Wu, Y., Yao, W.-X., Cao, Y., Wu, C., & Tanaka, M. (2006) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.05.010 · Cited by 61 · see citing works
Morrow, B. A., Elsworth, J. D., & Roth, R. H. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0708-0 · Cited by 61 · see citing works
Amino terminal domain regulation of NMDA receptor function
Herin, G. A., & Aizenman, E. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.07.015 · Cited by 55 · see citing works
Pinteaux, E., Copin, J.-C., Ledig, M., & Tholey, G. (2009) · Developmental Neuroscience · doi:10.1159/000111433 · Cited by 51 · cited 1× · see citing works
“Because the glutamatergic synapse is highly sensitive to oxidizing conditions (Kohr et al., 1994; Volterra et al., 1994; Pinteaux et al., 1996; Lipton et al., 2002; Herin 4 immunohistochemistry for PV and oxidized DHE fluorescence.”
Paterson, G., Ohashi, Y., Reynolds, G. P., Pratt, J. A., & MORRIS, B. J. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106062025 · Cited by 41 · see citing works
Oxidative Stress after Subarachnoid Hemorrhage in gp91phox Knockout Mice
Liu, S., Tang, J., Ostrowski, R. P., Titova, E., Monroe, C. E., Chen, W., Lo, W., Martin, R., & Zhang, J. H. (2007) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s031716710000682x · Cited by 32 · see citing works
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Interneuron dysfunction in psychiatric disorders
Marín, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3155 · Cited by 1,190 · see citing works
Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.001 · Cited by 1,178 · see citing works
Le Belle, J. E., Orozco, N. M., Paucar, A. A., Saxe, J. P., Mottahedeh, J., Pyle, A. D., Wu, H., & Kornblum, H. I. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.11.028 · Cited by 789 · see citing works
Fillman, S. G., Cloonan, N., Catts, V. S., Miller, L. C., Wong, J., McCrossin, T., Cairns, M., & Weickert, C. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.110 · Cited by 609 · see citing works
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
Behrens, M. M., Ali, S. S., Dao, D. N., Lucero, J., Shekhtman, G., Quick, K. L., & Dugan, L. L. (2007) · Science · doi:10.1126/science.1148045 · Cited by 585 · see citing works
Self-citationOxidative Stress and Psychological Disorders
Salim, S. (2014) · Current Neuropharmacology · doi:10.2174/1570159x11666131120230309 · Cited by 557 · see citing works
Neill, J. C., Barnes, S. A., Cook, S., Grayson, B., Idris, N. F., McLean, S. L., Snigdha, S., Rajagopal, L., & Harte, M. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.07.004 · Cited by 525 · see citing works
Oxidative stress in schizophrenia: An integrated approach
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.008 · Cited by 474 · see citing works
NOX Enzymes in the Central Nervous System: From Signaling to Disease
Sorce, S., & Krause, K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2578 · Cited by 472 · see citing works
Cytokines in bipolar disorder vs. healthy control subjects: A systematic review and meta-analysis
Munkholm, K., Braüner, J. V., Kessing, L. V., & Vinberg, M. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.05.018 · Cited by 402 · see citing works
Varnum, M. M., & Ikezu, T. (2012) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-012-0181-2 · Cited by 393 · see citing works
Redox dysregulation, neurodevelopment, and schizophrenia
Do, K. Q., Cabungcal, J. H., Frank, A., Steullet, P., & Cuenod, M. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.001 · Cited by 384 · see citing works
Steullet, P., Cabungcal, J.-H., Coyle, J., Didriksen, M., Gill, K., Grace, A. A., Hensch, T. K., LaMantia, A.-S., Lindemann, L., Maynard, T. M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.47 · Cited by 360 · see citing works
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Bansal, Y., & Kuhad, A. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160229114755 · Cited by 355 · see citing works
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Spooren, A., Kolmus, K., Laureys, G., Clinckers, R., De Keyser, J., Haegeman, G., & Gerlo, S. (2011) · Brain Research Reviews · doi:10.1016/j.brainresrev.2011.01.002 · Cited by 352 · see citing works
Alboni, S., Cervia, D., Sugama, S., & Conti, B. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-9 · Cited by 301 · see citing works
Solovyev, N. D. (2015) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2015.09.003 · Cited by 282 · see citing works
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Steullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., & Do, K. Q. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.021 · Cited by 262 · see citing works
Cytokines in bipolar disorder: A systematic review and meta-analysis
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Daniela, M., Luca, C. M., Onu, I., Paula, M., Iordan, D. A., & Buculei, I. (2022) · Antioxidants · doi:10.3390/antiox11020350 · Cited by 244 · see citing works
The neurobiology and treatment of first-episode schizophrenia
Kahn, R. S., & Sommer, I. E. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.66 · Cited by 219 · see citing works
NADPH oxidases: novel therapeutic targets for neurodegenerative diseases
Gao, H., Zhou, H., & Hong, J. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.03.008 · Cited by 212 · see citing works
Lanz, T. A., Reinhart, V., Sheehan, M. J., Rizzo, S. J. S., Bove, S. E., James, L. C., Volfson, D., Lewis, D. A., & Kleiman, R. J. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0492-8 · Cited by 209 · see citing works
Involvement of NOX2 in the Development of Behavioral and Pathologic Alterations in Isolated Rats
Schiavone, S., Sorce, S., Dubois-Dauphin, M., Jaquet, V., Colaianna, M., Zotti, M., Cuomo, V., Trabace, L., & Krause, K.-H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.04.033 · Cited by 208 · see citing works
Juvenile Antioxidant Treatment Prevents Adult Deficits in a Developmental Model of Schizophrenia
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Cytokine hypothesis of schizophrenia pathogenesis: Evidence from human studies and animal models
Watanabe, Y., Someya, T., & Nawa, H. (2010) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2010.02094.x · Cited by 204 · see citing works
Steullet, P., Cabungcal, J.-H., Kulak, A., Kraftsik, R., Chen, Y., Dalton, T. P., Cuenod, M., & Do, K. Q. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3857-09.2010 · Cited by 202 · see citing works
Parvalbumin interneuron vulnerability and brain disorders
Ruden, J. B., Dugan, L. L., & Konradi, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-0778-9 · Cited by 194 · see citing works
Self-citationInflammation in schizophrenia: A question of balance
Leza, J. C., García‐Bueno, B., Bioque, M., Arango, C., Parellada, M., Kim, Q., O’Donnell, P., & Bernardo, M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.014 · Cited by 183 · see citing works
Coughlin, J. M., Wang, Y., Ambinder, E. B., Ward, R. E., Minn, I., Vranešić, M., Kim, P. K., Ford, C. N., Higgs, C. P., Hayes, L. N., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.40 · Cited by 169 · see citing works
Powell, S. B., Sejnowski, T. J., & Behrens, M. M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.049 · Cited by 164 · see citing works
Self-citationMöller, M., du Preez, J. L., Viljoen, F. P., Berk, M., Emsley, R. A., & Harvey, B. H. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.12.011 · Cited by 168 · see citing works
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Dugan, L. L., Ali, S. S., Shekhtman, G., Roberts, A. J., Lucero, J., Quick, K. L., & Behrens, M. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005518 · Cited by 165 · see citing works
Self-citationBehrens, M. M., & B, T. J. S. A. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.06.002 · Cited by 160 · see citing works
Self-citationImplications for reactive oxygen species in schizophrenia pathogenesis
Koga, M., Serritella, A. V., Sawa, A., & Sedlak, T. W. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.06.022 · Cited by 159 · see citing works
NADPH oxidases in Parkinson’s disease: a systematic review
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Dwir, D., Giangreco, B., Xin, L., Tenenbaum, L., Cabungcal, J.-H., Steullet, P., Goupil, A., Cleusix, M., Jenni, R., Chtarto, A., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0393-5 · Cited by 137 · see citing works
Eastman, C. L., D’Ambrosio, R., & Ganesh, T. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107907 · Cited by 137 · see citing works
The Cytokine Model of Schizophrenia: Emerging Therapeutic Strategies
Girgis, R. R., Kumar, S. S., & Brown, A. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.12.002 · Cited by 135 · see citing works
Jiang, Z., Rompala, G. R., Zhang, S., Cowell, R. M., & Nakazawa, K. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.004 · Cited by 128 · see citing works
Which NADPH Oxidase Isoform Is Relevant for Ischemic Stroke? The Case for Nox 2
Kahles, T., & Brandes, R. P. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4721 · Cited by 125 · see citing works
Neurobiological Consequences of Sleep Deprivation
Alkadhi, K. A., Zagaar, M. A., Alhaider, I. A., Salim, S., & Aleisa, A. M. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311030001 · Cited by 121 · see citing works
Girgis, R. R., Ciarleglio, A., Choo, T. H., Haynes, G., Bathon, J. M., Cremers, S., Kantrowitz, J. T., Lieberman, J. A., & Brown, A. S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.258 · Cited by 119 · see citing works
Selenium, selenoprotein P, and Alzheimer's disease: is there a link?
Solovyev, N. D., Drobyshev, E. J., Bjørklund, G., Dubrovskii, Y. A., Lysiuk, R., & Rayman, M. P. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.030 · Cited by 114 · see citing works
Khan, A., Vaibhav, K., Javed, H., Tabassum, R., Ahmed, M. E., Khan, M. M., Khan, M. B., Shrivastava, P., Islam, F., Siddiqui, M. S., et al. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1231-9 · Cited by 110 · see citing works
Mismatch negativity as a biomarker of theta band oscillatory dysfunction in schizophrenia
Javitt, D. C., Lee, M., Kantrowitz, J. T., & Martı́nez, A. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.06.023 · Cited by 112 · see citing works
Neuroendocrine profile in a rat model of psychosocial stress: Relation to oxidative stress
Colaianna, M., Schiavone, S., Zotti, M., Tucci, P., Morgese, M. G., Bäckdahl, L., Holmdahl, R., Krause, K.-H., Cuomo, V., & Trabace, L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4569 · Cited by 107 · see citing works
Inflammation, mitochondria, and the inhibition of adult neurogenesis
Voloboueva, L. A., & Giffard, R. G. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22768 · Cited by 106 · see citing works
Garcia-Oscos, F., Salgado, H., Hall, S., Thomas, F., Farmer, G. E., Bermeo, J., Galindo, L. C., Ramirez, R. D., D'Mello, S., Rose-John, S., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.11.018 · Cited by 105 · see citing works
Kooijman, E., Nijboer, C. H. A., van Velthoven, C. T. J., Kavelaars, A., Kesecioğlu, J., & Heijnen, C. J. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-2 · Cited by 99 · see citing works
Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment
Reale, M., Costantini, E., & Greig, N. H. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.536257 · Cited by 98 · see citing works
NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress
Diebold, B. A., Smith, S. M., Yang, L., & Lambeth, J. D. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5862 · Cited by 96 · see citing works
Pharmacological Regulation of Oxidative Stress in Stem Cells
Lee, J., Cho, Y. S., Jung, H., & Choi, I. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/4081890 · Cited by 94 · see citing works
Sorce, S., Schiavone, S., Tucci, P., Colaianna, M., Jaquet, V., Cuomo, V., Dubois‐Dauphin, M., Trabace, L., & Krause, K. H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1491-10.2010 · Cited by 92 · see citing works
Jiang, Z., Cowell, R. M., & Nakazawa, K. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00116 · Cited by 89 · see citing works
Hong, J., & Bang, M. (2020) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2020.18.1.10 · Cited by 90 · see citing works
Estrogens and the cognitive symptoms of schizophrenia: Possible neuroprotective mechanisms
McGregor, C., Riordan, A. J., & Thornton, J. E. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.06.003 · Cited by 88 · see citing works
Munkholm, K., Weikop, P., Kessing, L. V., & Vinberg, M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.021 · Cited by 83 · see citing works
Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant
Zhu, W., Ding, Z., Zhang, Y., Shi, J., Hashimoto, K., & Lu, L. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0081-2 · Cited by 80 · see citing works
Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates
Dugan, L. L., Tian, L., Quick, K. L., Hardt, J. I., Karimi, M., Brown, C., Loftin, S. K., Flores, H., Moerlein, S. M., Polich, J. M., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24220 · Cited by 80 · see citing works
Self-citationThe role of glutamatergic inputs onto parvalbumin-positive interneurons: relevance for schizophrenia
Rotaru, D. C., Lewis, D. A., & González‐Burgos, G. (2012) · Reviews in the Neurosciences · doi:10.1515/revneuro-2011-0059 · Cited by 80 · see citing works
Ben‐Azu, B., Aderibigbe, A. O., Ajayi, A. M., Eneni, A.-E. O., Umukoro, S., & Iwalewa, E. O. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.03.006 · Cited by 79 · see citing works
Particulate Matter Induces Tissue OxInflammation: From Mechanism to Damage
Valacchi, G., Magnani, N., Woodby, B. L., Ferreira, S. M., & Evelson, P. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.8015 · Cited by 79 · see citing works
Ji, M.-H., Qiu, L., Tang, H., Ju, L.-S., Sun, X.-R., Zhang, H., Jia, M., Zuo, Z., Shen, J.-C., & Yang, J. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0401-x · Cited by 79 · see citing works
Li, Y., Shen, R., Wen, G., Ding, R., Du, A., Zhou, J., Dong, Z., Ren, X., Yao, H., Zhao, R., et al. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00139 · Cited by 80 · see citing works
Targeting NOX enzymes in the central nervous system: therapeutic opportunities
Sorce, S., Krause, K., & Jaquet, V. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1014-5 · Cited by 78 · see citing works
Li, B., Bedard, K., Sorce, S., Hinz, B., Dubois‐Dauphin, M., & Krause, K. (2009) · Journal of Innate Immunity · doi:10.1159/000235563 · Cited by 77 · see citing works
Prostate Cancer and Neuroendocrine Differentiation: More Neuronal, Less Endocrine?
Grigore, A. D., Ben‐Jacob, E., & Farach‐Carson, M. C. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00037 · Cited by 76 · see citing works
NADPH oxidase elevations in pyramidal neurons drive psychosocial stress-induced neuropathology
Schiavone, S., Jaquet, V., Sorce, S., Dubois‐Dauphin, M., Hultqvist, M. H., Bäckdahl, L., Holmdahl, R., Colaianna, M., Cuomo, V., Trabace, L., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.36 · Cited by 75 · see citing works
Tse, M., Piantadosi, P. T., & Floresco, S. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.09.007 · Cited by 73 · see citing works
Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia
Coyle, J. T., Balu, D. T., Benneyworth, M. A., Basu, A. C., & Roseman, A. S. (2010) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2010.12.3/jcoyle · Cited by 75 · see citing works
Inhibitory Interneurons, Oxidative Stress, and Schizophrenia
Sullivan, E. M., & O'Donnell, P. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs052 · Cited by 71 · see citing works
Prenatal maternal immune disruption and sex-dependent risk for psychoses
Goldstein, J. M., Cherkerzian, S., Seidman, L. J., Donatelli, J.-A. L., Remington, A., Tsuang, M. T., Hornig, M., & Buka, S. L. (2014) · Psychological Medicine · doi:10.1017/s0033291714000683 · Cited by 71 · see citing works
Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases
Korczowska-Łącka, I., Słowikowski, B. K., Piekut, T., Hurła, M., Banaszek, N., Szymanowicz, O., Jagodziński, P. P., Kozubski, W. P., Permoda-Pachuta, A., & Dorszewska, J. (2023) · Antioxidants · doi:10.3390/antiox12101811 · Cited by 76 · see citing works
Kalmady, S. V., Venkatasubramanian, G., Shivakumar, V., Gautham, S., Subramaniam, A., Jose, D. A., Maitra, A., Ravi, V., & Gangadhar, B. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096021 · Cited by 69 · see citing works
Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone
de Souza, D. F., Wartchow, K. M., Hansen, F., Lunardi, P. S., Guerra, M. C., Nardin, P., & Gonçalves, C. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.12.001 · Cited by 69 · see citing works
Pitts, M. W., Raman, A. V., Hashimoto, A. C., Todorovic, C., Nichols, R. A., & Berry, M. J. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.017 · Cited by 67 · see citing works
Rao, V. S. N., Carvalho, A. C. S., Trevisan, M. T. S., de Andrade, G. M., Júnior, H. V. N., de Moraes, M. O., Iury, H. I. M. H., Morais, T. C., & Santos, F. A. (2012) · Pharmacological Reports · doi:10.1016/s1734-1140(12)70879-4 · Cited by 66 · see citing works
Hamdani, N., Daban, C., Lajnef, M., Gadel, R., Corvoisier, P. L., Delavest, M., Carde, S., Lépine, J., Jamain, S., Houenou, J., et al. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.03.038 · Cited by 65 · see citing works
The Use of microRNAs to Modulate Redox and Immune Response to Stroke
Ouyang, Y., Stary, C. M., White, R., & Giffard, R. G. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5757 · Cited by 60 · see citing works
Magnani, N., Marchini, T., Calabró, V., Álvarez, S., & Evelson, P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.568305 · Cited by 64 · see citing works
Deslauriers, J., Larouche, A., Sarret, P., & Grignon, S. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.05.006 · Cited by 61 · see citing works
Neuroglialpharmacology: white matter pathophysiologies and psychiatric treatments
Bartzokis, G. (2011) · Frontiers in bioscience · doi:10.2741/3881 · Cited by 60 · see citing works
Möller, M., Swanepoel, T., & Harvey, B. H. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn5003368 · Cited by 59 · see citing works
Ben‐Azu, B., Emokpae, O., Ajayi, A. M., Jarikre, T. A., Orhode, V., Aderibigbe, A. O., Umukoro, S., & Iwalewa, E. O. (2020) · Brain Research · doi:10.1016/j.brainres.2020.146917 · Cited by 57 · see citing works
Feleder, C., Tseng, K. Y., Calhoon, G. G., & O'Donnell, P. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.028 · Cited by 57 · see citing works
Voloboueva, L. A., Lee, S. W., Emery, J. F., Palmer, T. D., & Giffard, R. G. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1752-10.2010 · Cited by 57 · see citing works
Hall, D. J., Han, S.-H., Chepetan, A. M., Inui, E. G., Rogers, M., & Dugan, L. L. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.119 · Cited by 56 · see citing works
Self-citationMansur, R. B., Zugman, A., Asevedo, E. D. M., da Cunha, G. R., Bressan, R. A., & Brietzke, E. M. (2012) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2012.02354.x · Cited by 55 · see citing works
Schiavone, S., Mhillaj, E., Neri, M., Morgese, M. G., Tucci, P., Bove, M., Valentino, M., Di Giovanni, G., Pomara, C., Turillazzi, E., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-9791-8 · Cited by 55 · see citing works
Liu, F., Yang, L., Sun, X., Zhang, H., Pan, W. X., Wang, X., Yang, J., Ji, M., & Yuan, H. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9571-x · Cited by 54 · see citing works
Ribonucleic Acid Interference Knockdown of Interleukin 6 Attenuates Cold-Induced Hypertension
Crosswhite, P. L., & Sun, Z. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.146902 · Cited by 53 · see citing works
Long-term effects of ionising radiation on the brain: cause for concern?
Kempf, S. J., Azimzadeh, O., Atkinson, M. J., & Tapio, S. (2012) · Radiation and Environmental Biophysics · doi:10.1007/s00411-012-0436-7 · Cited by 52 · see citing works
O’Donnell, P. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.07.005 · Cited by 52 · see citing works
Ben‐Azu, B., Omogbiya, I. A., Aderibigbe, A. O., Umukoro, S., Ajayi, A. M., & Iwalewa, E. O. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.02.007 · Cited by 52 · see citing works
Transcriptomic evidence for immaturity of the prefrontal cortex in patients with schizophrenia
Hagihara, H., Ohira, K., Takao, K., & Miyakawa, T. (2014) · Molecular Brain · doi:10.1186/1756-6606-7-41 · Cited by 52 · see citing works
Filipović, D., Stanisavljević, A., Jasnic, N. I., Bernardi, R. E., Inta, D., Perić, I., & Gass, P. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.12.020 · Cited by 49 · see citing works
- Authors
- Behrens, M. M., Ali, S. S., & Dugan, L. L.
- Affiliations
- University of California San Diego (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-12-17
- Volume
- 28
- Issue
- 51
- Pages
- 13957-13966
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2752712
- OpenAlex
- W2062030838
- Cited by
- 241
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 14 · 2019: 8 · 2018: 13 · 2017: 13 · 2016: 18 · 2015: 20 · 2014: 23 · 2013: 17 · 2012: 28
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hartford Foundation for Public Giving
- Larry L. Hillblom Foundation
- National Institute on Aging (K25AG026379, R21AG030320)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- interleukin-6, NADPH oxidase, ketamine, schizophrenia, NMDA receptor antagonists, superoxide, parvalbumin interneurons, fast-spiking interneurons, GABAergic interneurons, antioxidant defense, cytokine inhibition, IL-6-deficient mice
- MeSH terms
- Animals, Antibodies, Cells, Cultured, Disease Models, Animal, Enzyme Activation, gamma-Aminobutyric Acid, Interneurons, Ketamine, Male, Mice, Inbred C57BL, RNA, Messenger, Schizophrenia, Superoxides, Interleukin-6, Prefrontal Cortex, Mice, Knockout, NADPH Oxidases, Mice
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