Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheime...

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Main Authors:	Alexander Levit, Sonny Cheng, Olivia Hough, Qingfan Liu, Yuksel Agca, Cansu Agca, Vladimir Hachinski, Shawn N. Whitehead
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2020-04-01
Series:	Frontiers in Aging Neuroscience
Subjects:	hypertension amyloid astrocytes microglia white matter cognitive function
Online Access:	https://www.frontiersin.org/article/10.3389/fnagi.2020.00082/full

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spelling	doaj-00c19104ec884a9099fd1f494c73d4f82020-11-25T02:30:13ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-04-011210.3389/fnagi.2020.00082514544Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the RatAlexander Levit0Sonny Cheng1Olivia Hough2Qingfan Liu3Yuksel Agca4Cansu Agca5Vladimir Hachinski6Shawn N. Whitehead7Shawn N. Whitehead8Vulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaDepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, United StatesDepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, United StatesDepartment of Clinical Neurological Sciences, University Hospital, Western University, London, ON, CanadaVulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaDepartment of Clinical Neurological Sciences, University Hospital, Western University, London, ON, CanadaHypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats’ executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.https://www.frontiersin.org/article/10.3389/fnagi.2020.00082/fullhypertensionamyloidastrocytesmicrogliawhite mattercognitive function
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Alexander Levit Sonny Cheng Olivia Hough Qingfan Liu Yuksel Agca Cansu Agca Vladimir Hachinski Shawn N. Whitehead Shawn N. Whitehead
spellingShingle	Alexander Levit Sonny Cheng Olivia Hough Qingfan Liu Yuksel Agca Cansu Agca Vladimir Hachinski Shawn N. Whitehead Shawn N. Whitehead Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat Frontiers in Aging Neuroscience hypertension amyloid astrocytes microglia white matter cognitive function
author_facet	Alexander Levit Sonny Cheng Olivia Hough Qingfan Liu Yuksel Agca Cansu Agca Vladimir Hachinski Shawn N. Whitehead Shawn N. Whitehead
author_sort	Alexander Levit
title	Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat
title_short	Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat
title_full	Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat
title_fullStr	Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat
title_full_unstemmed	Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat
title_sort	hypertension and pathogenic happ independently induce white matter astrocytosis and cognitive impairment in the rat
publisher	Frontiers Media S.A.
series	Frontiers in Aging Neuroscience
issn	1663-4365
publishDate	2020-04-01
description	Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats’ executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.
topic	hypertension amyloid astrocytes microglia white matter cognitive function
url	https://www.frontiersin.org/article/10.3389/fnagi.2020.00082/full
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Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

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