Abstract
The renin angiotensin system (RAS) plays a major role in cardiovascular disease. Novel metabolic pathways of the RAS offer new therapeutic targets for disease prevention. Recent studies demonstrated a novel binding site for the active hormone of the RAS: angiotensin II (Ang II). This binding site, now known to be the enzyme neurolysin, can metabolize Ang II into inactive fragments and act upon a precursor of Ang II (Ang I) to circumvent Ang II production. Radioligand binding and histological techniques were utilized to assay neurolysin and the primary receptors for Ang II (AT1, and AT2) in normal (wild-type) and neurolysin knockout mouse brains. Autoradiograms show that neurolysin is widely distributed in the mouse brain with high expression in areas associated with drug addiction, Parkinson’s, and Alzheimer’s disease (nucleus accumbens, substantia nigra, and hippocampus). Radioligand binding in the neurolysin knockout brains was reduced by 46%. Residual binding of the radioligand suggests there may be another novel Ang II binding site in the mouse brain. Primary receptors for Ang II in the neurolysin knockout brains were also reduced. There was a 56% increase in lateral ventricle size of the knockout mouse brains suggestive of hydrocephalus, a condition characterized by excessive fluid accumulation in the brain leading to mental retardation. Since the RAS is a major regulator of fluid and electrolyte balance in the body, loss of neurolysin may adversely affect cerebrospinal fluid regulation. Future studies will be directed towards determining the importance of neurolysin for blood pressure regulation and neuropsychological function.
Faculty Sponsors
Dr. Robert Speth, Dr. Mark Jaffe
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-12-2013 1:00 PM
End Date
4-12-2013 5:30 PM
The Importance of Neurolysin in the Renin-Angiotensin System of the Mouse Brain
Alvin Sherman Library
The renin angiotensin system (RAS) plays a major role in cardiovascular disease. Novel metabolic pathways of the RAS offer new therapeutic targets for disease prevention. Recent studies demonstrated a novel binding site for the active hormone of the RAS: angiotensin II (Ang II). This binding site, now known to be the enzyme neurolysin, can metabolize Ang II into inactive fragments and act upon a precursor of Ang II (Ang I) to circumvent Ang II production. Radioligand binding and histological techniques were utilized to assay neurolysin and the primary receptors for Ang II (AT1, and AT2) in normal (wild-type) and neurolysin knockout mouse brains. Autoradiograms show that neurolysin is widely distributed in the mouse brain with high expression in areas associated with drug addiction, Parkinson’s, and Alzheimer’s disease (nucleus accumbens, substantia nigra, and hippocampus). Radioligand binding in the neurolysin knockout brains was reduced by 46%. Residual binding of the radioligand suggests there may be another novel Ang II binding site in the mouse brain. Primary receptors for Ang II in the neurolysin knockout brains were also reduced. There was a 56% increase in lateral ventricle size of the knockout mouse brains suggestive of hydrocephalus, a condition characterized by excessive fluid accumulation in the brain leading to mental retardation. Since the RAS is a major regulator of fluid and electrolyte balance in the body, loss of neurolysin may adversely affect cerebrospinal fluid regulation. Future studies will be directed towards determining the importance of neurolysin for blood pressure regulation and neuropsychological function.
