Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease.
J Cereb Blood Flow Metab
; 37(7): 2396-2413, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-27596834
ABSTRACT
Elevated angiotensin II causes hypertension and contributes to Alzheimer's disease by affecting cerebral blood flow. Angiotensin II receptor blockers may provide candidates to reduce (vascular) risk factors for Alzheimer's disease. We studied effects of two months of angiotensin II-induced hypertension on systolic blood pressure, and treatment with the angiotensin II receptor blockers, eprosartan mesylate, after one month of induced hypertension in wild-type C57bl/6j and AßPPswe/PS1ΔE9 (AßPP/PS1/Alzheimer's disease) mice. AßPP/PS1 showed higher systolic blood pressure than wild-type. Subsequent eprosartan mesylate treatment restored this elevated systolic blood pressure in all mice. Functional connectivity was decreased in angiotensin II-infused Alzheimer's disease and wild-type mice, and only 12 months of Alzheimer's disease mice showed impaired cerebral blood flow. Only angiotensin II-infused Alzheimer's disease mice exhibited decreased spatial learning in the Morris water maze. Altogether, angiotensin II-induced hypertension not only exacerbated Alzheimer's disease-like pathological changes such as impairment of cerebral blood flow, functional connectivity, and cognition only in Alzheimer's disease model mice, but it also induced decreased functional connectivity in wild-type mice. However, we could not detect hypertension-induced overexpression of Aß nor increased neuroinflammation. Our findings suggest a link between midlife hypertension, decreased cerebral hemodynamics and connectivity in an Alzheimer's disease mouse model. Eprosartan mesylate treatment restored and beneficially affected cerebral blood flow and connectivity. This model could be used to investigate prevention/treatment strategies in early Alzheimer's disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
Comportamento Animal
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Encéfalo
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Angiotensina II
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Antagonistas de Receptores de Angiotensina
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Doença de Alzheimer
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Hipertensão
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Imidazóis
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Holanda