Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells to Neurons in Different Brain Areas

Autor: Rafael Calixto Bortolin, Daniel Pens Gelain, Thallita Kelly Rabelo, Camila Tiefensee Ribeiro, José Cláudio Fonseca Moreira, Juciano Gasparotto, Daniel Oppermann Peixoto, Helen Tais da Rosa-Silva
Rok vydání: 2018
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_specialty
Tyrosine 3-Monooxygenase
endocrine system diseases
Receptor for Advanced Glycation End Products
Neuroscience (miscellaneous)
Substantia nigra
Inflammation
Systemic inflammation
RAGE (receptor)
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Internal medicine
medicine
Animals
cardiovascular diseases
Rats
Wistar
Receptor
Neuroinflammation
Neurons
Chemistry
Cell adhesion molecule
Dopaminergic Neurons
Neurodegeneration
Brain
Endothelial Cells
nutritional and metabolic diseases
medicine.disease
Platelet Endothelial Cell Adhesion Molecule-1
Substantia Nigra
030104 developmental biology
Endocrinology
Neurology
cardiovascular system
medicine.symptom
human activities
Biomarkers
030217 neurology & neurosurgery
Zdroj: Molecular Neurobiology. 56:3079-3089
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-018-1291-6
Popis: 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.
Databáze: OpenAIRE
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