Receptor for Advanced Glycation End Products (RAGE) is Expressed Predominantly in Medium Spiny Neurons of tgHD Rat Striatum.

Neuroscience

Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Department of Neuroscience, Baylor College of Medicine, 1250 Moursund St, Houston, TX 77030, United States. Electronic address:

Published: June 2018

AI Article Synopsis

  • RAGE is a receptor linked to several neurodegenerative diseases, including Huntington's disease (HD), with previous studies showing its levels increase in relation to disease severity in HD patients.
  • A study on transgenic HD rats revealed that while RAGE expression was higher in the affected brain region compared to normal rats, this expression did not change with disease severity.
  • The findings suggest that RAGE expression patterns in the rat model do not fully align with those observed in human HD brains, questioning the model's effectiveness for future research.

Article Abstract

Receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in the pathology of several progressive neurodegenerative disorders including Huntington's disease (HD). We previously showed that the expression of RAGE and its colocalization with ligands were increased in the striatum of HD patients, increasing with grade severity, and that the pattern of RAGE expression coincided with the medio-lateral pattern of neurodegeneration. However, the exact role of RAGE in HD remains elusive. In order to address the necessity for a direct functional study, we aimed to characterize the pattern of RAGE expression in the transgenic rat model of HD (tgHD rats). Our results showed that RAGE expression was expanded laterally in tgHD rat caudate-putamen (CPu) compared to wildtype littermates, but the expression was unchanged by disease severity. The rostro-caudal location did not affect RAGE expression. RAGE was predominantly expressed in the medium spiny neurons (MSN) where it colocalized most extensively with N-carboxymethyllysine (CML), which largely contradicts with observations from human HD brains. Overall, the tgHD rat model only partially recapitulated the pattern in striatal RAGE expression in human brains, raising a question about its reliability as an animal model for future functional studies.

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http://dx.doi.org/10.1016/j.neuroscience.2018.03.042DOI Listing

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