Faculty, Staff and Student Publications
Publication Date
7-12-2022
Journal
International Journal of Molecular Sciences
Abstract
The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington's disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside a decrease in the levels and activity of the components of the RAS alternative axis ACE2, Ang-(1-7), and Mas receptors in the striatum, prefrontal cortex, and hippocampus. BACHD mice also displayed a significant increase in mRNA expression of the AT1 receptor, a component of the RAS classical arm, in these key brain regions. Moreover, patients with manifest HD presented higher plasma levels of Ang-(1-7). No significant changes were found in the levels of ACE, ACE2, and Ang II. Our findings provided the first evidence that an imbalance in the RAS classical and counter-regulatory arms may play a role in HD pathophysiology.
Keywords
Angiotensin I, Angiotensin II, Angiotensin-Converting Enzyme 2, Animals, Disease Models, Animal, Humans, Huntington Disease, Mice, Peptide Fragments, Peptidyl-Dipeptidase A, Receptor, Angiotensin, Type 1, Renin-Angiotensin System, Huntington’s disease, renin-angiotensin system, BACHD, angiotensin peptides
DOI
10.3390/ijms23147686
PMID
35887034
PMCID
PMC9316902
PubMedCentral® Posted Date
7-12-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Medical Molecular Biology Commons, Neurology Commons