Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction
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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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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).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Tong et al., 2008
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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)
- PMC
- PMC4052889
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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