Cited by 223Nerve injury and regenerationNeuroinflammation and Neurodegeneration MechanismsCytokine Signaling Pathways and Interactions

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

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Tong, Liqi, Balazs, Robert, Soiampornkul, Rungtip, Thangnipon, Wipawan, Cotman, Carl W.·2008·Neurobiology of Aging

Abstract

The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1 beta renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1 beta compromised the PI3-K/Akt pathway-mediated protection by BDNF and suppressed Akt activation. The effect was specific as in addition to Akt, the activation of MAPK/ERK, but not PLC gamma, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1 beta. As the cytokine did not influence TrkB receptor and PLC gamma activation, IL-1 beta might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1 beta suppressed the activation of the respective scaffolding proteins IRS-1 and Shc; this effect might involve ceramide generation. IL-1-induced interference with BDNF neuroprotection and signal transduction was corrected, in part, by ceramide production inhibitors and mimicked by the cell-permeable C2-ceramide. These results suggest that IL-1 beta places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism.

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Crossref · 10.1016/j.neurobiolaging.2007.02.027

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84 of 84 references verified0 citation errors · 0 not checkable

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  • IFN-alpha administration decreases systemic BDNF levels in humans, as do other inflammatory cytokines and LPS injections.

    “IFN-alpha administration has also been found to decrease systemic BDNF levels in humans (Kenis et al., 2010, Lotrich et al., 2013) (see Figure 1), as can other inflammatory cytokines and LPS injections (Tong et al., 2008, Cortese et al., 2011) (Guan and Fang, 2006).”

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Authors
Tong, L., Balazs, R., Soiampornkul, R., Thangnipon, W., & Cotman, C. W.
Affiliations
  • University of California, Irvine (US)
  • Mahidol University (TH)
Corresponding author
Tong, Liqi
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2008-09
Volume
29
Issue
9
Pages
1380-1393
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2015851283
Cited by
222
References
88
Citations by year
2026: 9 · 2025: 10 · 2024: 18 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 14 · 2017: 18 · 2016: 13 · 2015: 8 · 2014: 11 · 2013: 18 · 2012: 15
FWCI
2.79
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (P01AG000538)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
IL-1β, brain-derived neurotrophic factor, neuroprotection, PI3K/Akt signaling, ERK signaling, CREB activation, TrkB receptor, IRS-1, Shc, ceramide, neurodegeneration, Alzheimer's disease, neuroinflammation, signal transduction
MeSH terms
Animals, Cells, Cultured, Cerebral Cortex, Neurons, Signal Transduction, Apoptosis, Brain-Derived Neurotrophic Factor, Rats, Interleukin-1beta

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