OS 25-06 CENTRAL ANGIOTENSIN II ACCELERATES BRAIN INJURY AND SARCOPENIA ASSOCIATED WITH OXIDATIVE STRESS IN A MOUSE MODEL OF ALZHEMIER'S DISEASE.

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Abstract

Objective:

Increasing evidences suggest that patients with Alzheimer's disease (AD) show not only cognitive impairment but also physical disorder including cardiac dysfunction and sarcopenia. In this study, we investigated whether central angiotensin II, inducer of oxidative stress, led to the organ dysfunction in a mouse model of AD.

Design and Method:

5XFAD which is an animal model of AD and C57BL/6 (WT) were each assigned to 1) normal saline and 2) angiotensin II (20 mg/kg/h) groups. Those solutions were infused intracerebroventricularly for 28 days. The changes of blood pressure, body weight, food and water intake, urinary volume, rotarod test, and watermaze test were monitored at appropriate time point. At 28 days after the start of the intracerebral infusion, weights of their brain, left ventricle, and gastrocnemius muscle were measured and histological evaluations which were related to oxidative stress and amyloid β protein (Aβ) deposition were conducted.

Results:

Angiotensin II increased blood pressure and decreased body weight, whereas food intake was not changed among the groups. Although angiotensin II deteriorated motor function detected by rotarod test in 5XFAD, it showed similar effect in cognitive impairment both WT and 5XFAD without brain atrophy. On the other hand, histological evaluation revealed that angiotensin II did not increase hippocampal superoxide and macrophage expressions in WT, but upregulated them in 5XFAD without loading of Ab deposition. In addition, angiotensin II induced cardiac hypertrophy and cardiomyocyte fibrosis in WT, while atrophy and upregulated macrophage expression by angiotensin II in gastrocnemius muscle were seen in 5XFAD.

Conclusions:

We suggest that central activation of RAS might play important roles in progression of brain injury and sarcopenia of AD patients.

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