Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia
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Background: Activation of the peripheral innate immune system stimulates the secretion of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive production of cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, an anti-inflammatory agent and purported microglial inhibitor, attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. Methods: In the first set of experiments the effect of minocycline pretreatment on LPS-induced microglia activation was assessed in BV-2 microglia cell cultures. In the second study, adult (3–6 m) BALB/c mice received an intraperitoneal (i.p.) injection of vehicle or minocycline (50 mg/kg) for three consecutive days. On the third day, mice were also injected (i.p.) with saline or Escherichia coli LPS (0.33 mg/kg) and behavior (i.e., sickness and anhedonia) and markers of neuroinflammation (i.e., microglia activation and inflammatory cytokines) were determined. In the final study, adult and aged BALB/c mice were treated with the same minocycline and LPS injection regimen and markers of neuroinflammation were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions. Results: Minocycline blocked LPS-stimulated inflammatory cytokine secretion in the BV-2 microglia-derived cell line and reduced LPS-induced Toll-like-receptor-2 (TLR2) surface expression on brain microglia. Moreover, minocycline facilitated the recovery from sickness behavior (i.e., anorexia, weight loss, and social withdrawal) and prevented anhedonia in adult mice challenged with LPS. Furthermore, the minocycline associated recovery from LPS-induced sickness behavior was paralleled by reduced mRNA levels of Interleukin (IL)-1β, IL-6, and indoleamine 2, 3 dioxygenase (IDO) in the cortex and hippocampus. Finally, in aged mice, where exaggerated neuroinflammation was elicited by LPS, minocycline pretreatment was still effective in markedly reducing mRNA levels of IL-1β, TLR2 and IDO in the hippocampus. Conclusion: These data indicate that minocycline mitigates neuroinflammation in the adult and aged brain and modulates the cytokine-associated changes in motivation and behavior.
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Minocycline reduced LPS-induced augmentation of inflammatory mediators, such as IL-1β, indoleamine 2,3 dioxygenase and TLR2, indicating that the neuroinflammatory response and sickness behavior following LPS is mediated by microglial activation.
“In addition, minocycline, a tetracycline antibiotic with anti-inflammatory actions on microglia, reduced LPS-induced augmentation of inflammatory mediators, such as IL-1β, indoleamine 2,3 dioxygenase and TLR2, indicating that the neuroinflammatory response and sickness behavior following LPS is mediated by microglial activation (Henry et al, 2008).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Henry et al, 2008
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- Authors
- Henry, C. J., Huang, Y., Wynne, A., Hanke, M., Himler, J., Bailey, M. T., Sheridan, J. F., & Godbout, J. P.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Godbout, Jonathan P
- Venue
- Journal of Neuroinflammation
- Published
- 2008-05-13
- Volume
- 5
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC2412862
- OpenAlex
- W2127854743
- Cited by
- 678
- References
- 72
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 35 · 2023: 31 · 2022: 41 · 2021: 59 · 2020: 46 · 2019: 33 · 2018: 42 · 2017: 39 · 2016: 55 · 2015: 47 · 2014: 36 · 2013: 38 · 2012: 34
- FWCI
- 16.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH T32)
- National Institute on Aging (R01AG033028)
- National Institute of Mental Health (R21MH077817, R03MH076786)
- National Institute of Allergy and Infectious Diseases (T32AI055411)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- lipopolysaccharide, neuroinflammation, sickness behavior, anhedonia, microglial activation, TLR2, inflammatory cytokines, IL-1β, interleukin-6, indoleamine 2,3-dioxygenase, BV-2 cells, aged mice
- MeSH terms
- Age Factors, Animals, Cell Line, Cerebral Cortex, Drug Evaluation, Preclinical, Endotoxins, Exploratory Behavior, Food Preferences, Hippocampus, Male, Mice, Inbred BALB C, Minocycline, RNA, Messenger, Sick Role, Social Behavior Disorders, Specific Pathogen-Free Organisms, Interleukin-6, Microglia, Dietary Sucrose, Endotoxemia, Mood Disorders, Toll-Like Receptor 2, Mice, Interleukin-1beta
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