The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia
Open accessAbstract
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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“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]
In the citing paper
“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]
In the citing paper
“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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Citations
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
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
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
Jentsch, J. D. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00060-8 · Cited by 1,329
Homayoun, H., & Moghaddam, B. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2213-07.2007 · Cited by 1,231
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
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
Akbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002
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
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
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Solh, T., & Cevher, Ş. C. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115528 · Cited by 8
Chen, Q., Wang, K., Jiang, D., Wang, Y., Xiao, X., Zhu, N., Li, M., Jia, S., & Wang, Y. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1862-8 · Cited by 7
Aksic, M., Jakovčevski, I., Hamad, M. I. K., Jakovljevic, V. L., Stankovic, S. D., & Vulović, M. (2024) · Biomedicines · doi:10.3390/biomedicines12081726 · Cited by 5
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Dietrich‐Muszalska, A. (2014) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-1-4939-0440-2_2 · Cited by 5
Thomsen, M. S., Hansen, H. H., & Mikkelsen, J. D. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.08.013 · Cited by 4
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Ueno, H., Takahashi, Y., Murakami, S., Wani, K., Matsumoto, Y., Okamoto, M., & Ishihara, T. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.06.005 · Cited by 3
Zhuo, C., Hu, S., Chen, G., Yang, L., Cai, Z., Tian, H., Jiang, D., Chen, C., Wang, L., Ma, X., et al. (2023) · Schizophrenia · doi:10.1038/s41537-023-00400-w · Cited by 3
Liu, Y., Wang, Q., Wang, Q., Cui, M., Jin, Y., Wang, R., Mao, Z., Miao, D., Karaplis, A. C., Zhang, Y. P., et al. (2020) · Developmental Neurobiology · doi:10.1002/dneu.22798 · Cited by 3
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Abdel‐Salam, O. M. E., Youness, E. R., Sleem, A. A., & Omara, E. A. A. (2021) · WSEAS TRANSACTIONS ON BIOLOGY AND BIOMEDICINE · doi:10.37394/23208.2021.18.15 · Cited by 3
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Pan, S.-Y., Gu, Y.-R., Zhao, G., Wang, Y., Qin, Z., Tang, Q.-Y., Qin, Y., & Luo, L. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150360 · Cited by 2
Venkatasubramanian, G., Shivakumar, V., Sreeraj, V. S., Subbanna, M., Kalmady, S. V., Amaresha, A. C., Narayanaswamy, J., & Debnath, M. (2020) · Indian Journal of Psychiatry · doi:10.4103/psychiatry.indianjpsychiatry_486_19 · Cited by 2
Tan, X.-X., Ma, H., Guo, X., Mao, M., Qiu, L., Dai, H., Dai, Y., Cao, J., Ma, H., & Sun, J. (2023) · Neuroscience Letters · doi:10.1016/j.neulet.2023.137614 · Cited by 2
Geloso, M. C., Sante, G. D., & Granato, A. (2026) · Cells · doi:10.3390/cells15100869 · Cited by 1
Mead, E. (2012) · UCL Discovery (University College London) · Cited by 1
Corriveau, J. A. (2015) · OpenCommons at University of Connecticut (University of Connecticut)
Estrés Oxidativo y Esquizofrenia
Prados, A. B. (2014) · Gredos (University of Salamanca) · doi:10.14201/gredos.124073
Liu, F., Havens, J. F., Yu, Q., Wang, G., Davisson, R. L., Pickel, V. M., & Iadecola, C. (2012)
Gomes, F. V. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2016.tde-05012016-224242
Fulmer, T. (2010) · Science-Business eXchange · doi:10.1038/scibx.2010.1032
Balu, D. T., & GOFF, D. C. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9780511980053.005
Behrens, M. M. (2011) · Neuromethods · doi:10.1007/978-1-61779-157-4_6
Self-citationGuggilam, A. (2009) · Louisiana State University · doi:10.31390/gradschool_dissertations.1329
Nanotechnology in the Prevention and Treatment of Neurological Disorders
Kateb, B., Shapovalov, V. S., Mari, Z. K., Schmidt, P., Liker, M. A., Okereke, J., Sinclair, C., & Salimpour, Y. (2024) · Springer eBooks · doi:10.1007/978-3-030-80662-0_28
The Role of the Immune System in Creating Depression, Post-traumatic-Stress-Disorder, and Psychosis
Littrell, J. L. (2024) · Integrated science · doi:10.1007/978-3-031-72079-6_2
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Hu, J., Wang, P., Lin, Y., Jiang, Z., Zhang, Y., Shi, K., Wen, D., Ma, C., Liao, L., & Wang, X. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115337 · Cited by 1
Jakovčevski, I., Acar, A., Schwindenhammer, B., Hamad, M. I. K., Reiss, G., Förster, E., & Schachner, M. (2025) · Biomolecules · doi:10.3390/biom15091247
Ketamine-induced NMDA receptor hypofunction alters social and locomotor behavior in adult zebrafishPreprint
Gallas‐Lopes, M., Müller, D., Stahlhofer-Buss, T., Bastos, L. M., Becker, S. Z., Bruck, S. M., Piato, Â., & Herrmann, A. P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.16.676572
Ben-Azu, L., Onyeukwu, O. B., Chijioke, B. S., Oboh, M., Esuku, D. T., Adeleke, P. A., Onuelu, J. E., & Ben-Azu, B. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.02.055 · Cited by 2
Jézéquel, J. (2016) · theses.fr (ABES) · doi:10.70675/a7276087zc049z442fz8b5bzab9e03d034cb
He, Q., Wang, X., Zhang, X., & Shu, Y. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01303-0
Olfactory bulb 6-OHDA neurotoxicity as a model of early cortical dysfunction
Fiorenza‐Neto, E. A., Gattiboni, B. B., de Almeida, K., Marqueze, L. F., Mogharbel, B. F., de Aguiar, J. R. N., Marques, L. C., Lazarini, L. R., Carvalhal, S. R. S., Boldt, A. B. W., et al. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05591-1
Tukiran, N., Kolb, T., Maggioni, L., Rai, S., Rafath, Z., & Borsini, A. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.107069
Neuronal nicotinic receptors as targets for enhancing cognition in schizophrenia
Rushforth, S. L. (2013)
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Deslauriers, J., & Grignon, S. (2014) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-1-4939-0440-2_22
Metadata
- 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 (medical) › 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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