Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas
Abstract
The receptor for advanced glycation endproducts (RAGE) is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is considered a key receptor in the inflammation axis and a potential contributor to the neurodegeneration. The present study aimed to investigate the content and cell localization of RAGE in the brain of Wistar rats subjected to systemic inflammation induced by a single dose of lipopolysaccharide (LPS, 5 mg/kg, i.p.). Fifteen days after LPS administration, the content of RAGE was analyzed in the prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia nigra (SN) were investigated. RAGE levels increased in all structures, except HIPP; however, immunohistochemistry analysis demonstrated that the cell site of RAGE expression changed from blood vessel-like structures to neuronal cells in all brain areas. Besides, the highest level of RAGE expression was found in SN. Immunofluorescence analysis in SN confirmed that RAGE expression was mainly co-localized in endothelial cells (RAGE/PECAM-1 co-staining) in untreated animals, while LPS-treated animals had RAGE expression predominantly in dopaminergic neurons (RAGE/TH co-staining). Decreased TH levels, as well as increased pro-inflammatory markers (TNF-α, IL-1β, Iba-1, GFAP, and phosphorylated ERK1/2) in SN, occurred concomitantly to RAGE stimulation in the same site. These results suggest a role for RAGE in the establishment of a neuroinflammation-neurodegeneration axis that develops as a long-term response to systemic inflammation by LPS.
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RAGEs are significantly or markedly expressed in many areas of the brain, such as the cortex, hippocampus, cerebellum, and substantia nigra, during the development of neurodegenerative diseases.
“Similar to AGEs, RAGEs are significantly or markedly expressed in many areas of the brain, such as the cortex, hippocampus, cerebellum, and substantia nigra105–107 during the development of neurodegenerative diseases.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [106]
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- Authors
- Gasparotto, J., Ribeiro, C. T., da Rosa-Silva, H. T., Bortolin, R. C., Rabelo, T. K., Peixoto, D. O., Moreira, J. C. F., & Gelain, D. P.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Universidad de la Costa (CO)
- Universidade Federal de Sergipe (BR)
- Corresponding author
- Gasparotto, Juciano
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2018-08-09
- Volume
- 56
- Issue
- 5
- Pages
- 3079-3089
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2886601168
- Cited by
- 36
- References
- 32
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 3
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- DSPACE System - Metalibrary (University of the Coast) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- receptor for advanced glycation end products, RAGE, systemic inflammation, lipopolysaccharide, neuroinflammation, neurodegeneration, dopaminergic neurons, substantia nigra, endothelial cells, CD31, tyrosine hydroxylase, TNF-α, IL-1β, Iba1, glial fibrillary acidic protein, ERK1/2 phosphorylation, prefrontal cortex, hippocampus, cerebellum
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Brain, Inflammation, Lipopolysaccharides, Male, Neurons, Substantia Nigra, Tyrosine 3-Monooxygenase, Biomarkers, Rats, Wistar, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial Cells, Dopaminergic Neurons
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