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

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• The receptor for advanced glycation endproducts (RAGE) is a cell adhesion molecule implicated in inflammation and neurodegeneration.
• RAGE interacts with various extracellular ligands and plays a role in inflammatory pathways.

Purpose of the Study:

• To investigate the impact of systemic inflammation induced by lipopolysaccharide (LPS) on RAGE expression and localization in specific brain regions of Wistar rats.
• To explore the relationship between RAGE changes and neuroinflammatory markers in the substantia nigra.

Main Methods:

• Wistar rats were administered a single dose of LPS (5 mg/kg, i.p.) to induce systemic inflammation.
• Fifteen days post-LPS, RAGE content was analyzed in the prefrontal cortex, hippocampus, cerebellum, and substantia nigra.
• Immunohistochemistry and immunofluorescence were used to determine RAGE cell localization, co-localizing with endothelial (PECAM-1) and dopaminergic (TH) markers.

Main Results:

• RAGE levels increased in the prefrontal cortex, cerebellum, and substantia nigra, but not the hippocampus.
• RAGE expression shifted from endothelial cells to neuronal cells across all investigated brain areas.
• In the substantia nigra, RAGE predominantly localized to dopaminergic neurons post-LPS, alongside decreased tyrosine hydroxylase (TH) and increased pro-inflammatory markers (TNF-α, IL-1β, Iba-1, GFAP, p-ERK1/2).

Conclusions:

• Systemic inflammation induced by LPS leads to long-term changes in RAGE expression and localization within the rat brain.
• The findings suggest RAGE is involved in a neuroinflammation-neurodegeneration axis, particularly in the substantia nigra, as a consequence of systemic inflammation.