Protection of TGF-β1 against Neuroinflammation and Neurodegeneration in Aβ1–42-Induced Alzheimer’s Disease Model Rats
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Neuroinflammation has been reported to be associated with Alzheimer's disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)1-42. TGF-β1 was administered via ICV one hour prior to Aβ1-42 injection or via both nares seven days after Aβ1-42 injection. ICV administration of TGF-β1 before Aβ1-42 injection remarkably ameliorated Aβ1-42-induced neurodegeneration and prevented Aβ1-42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ1-42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ1-42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ1-42 neurotoxicity suggests a possible therapeutic approach in patients with AD.
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After Aβ1-42 injection, pro-inflammatory cytokines increase and anti-inflammatory cytokines and BDNF protein levels and gene expression decrease.
“Another study confirmed the increase in pro-inflammatory cytokines and reduced antiinflammatory cytokines and BDNF protein levels and gene expression after Aβ1–42 injection [155].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [155]
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- Authors
- Chen, J.-H., Ke, K.-F., Lu, J.-H., Qiu, Y.-H., & Peng, Y.-P.
- Affiliations
- Nantong University (CN)
- Corresponding author
- Peng, Yu-Ping
- ORCID
- Peng, Yu-Ping
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-02-06
- Volume
- 10
- Issue
- 2
- Pages
- e0116549
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4319949
- OpenAlex
- W2047256501
- Cited by
- 151
- References
- 55
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 11 · 2023: 9 · 2022: 10 · 2021: 17 · 2020: 20 · 2019: 12 · 2018: 18 · 2017: 10 · 2016: 14 · 2015: 4
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Rochester
- National Natural Science Foundation of China (31371182, 81271323)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- TGF-β1, Alzheimer's disease, neuroinflammation, neurodegeneration, amyloid-beta 42, Th17 cells, intranasal administration, intracerebroventricular administration, neuroprotection, neurotrophic factors, brain-derived neurotrophic factor, IL-10, inflammatory cytokines, glial activation, hypothalamus
- MeSH terms
- Administration, Intranasal, Alzheimer Disease, Animals, Anti-Inflammatory Agents, Disease Models, Animal, Hypothalamus, Inflammation, Injections, Nerve Degeneration, Neuroglia, Peptide Fragments, Cytokines, Amyloid beta-Peptides, Rats, Sprague-Dawley, Neuroprotective Agents, Rats, Transforming Growth Factor beta1
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