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

The receptor for advanced glycation endproducts is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. 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 duanyu1648 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 duanyu1648 was analyzed in the prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia nigra (SN) were investigated. duanyu1648 levels increased in all structures, except HIPP; however, immunohistochemistry analysis demonstrated that the cell site of duanyu1648 expression changed from blood vessel-like structures to neuronal cells in all brain areas. Besides, the highest level of duanyu1648 expression was found in SN. Immunofluorescence analysis in SN confirmed that duanyu1648 expression was mainly co-localized in endothelial cells co-staining) in untreated animals, while LPS-treated animals had duanyu1648 expression predominantly in dopaminergic neurons 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 duanyu1648 stimulation in the same site. These results suggest a role for duanyu1648 in the establishment of a neuroinflammation-neurodegeneration axis that develops as a long-term response to systemic inflammation by LPS.

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