Memory and cerebrovascular deficits recovered following angiotensin IV intervention in a mouse model of Alzheimer's disease.
Neurobiol Dis
; 134: 104644, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31669735
ABSTRACT
Angiotensin II type 1 receptor antagonists like losartan have been found to lower the incidence and progression to Alzheimer's disease (AD), as well as rescue cognitive and cerebrovascular deficits in AD mouse models. We previously found that co-administration of an angiotensin IV (AngIV) receptor (AT4R) antagonist prevented losartan's benefits, identifying AT4Rs as a possible target to counter AD pathogenesis. Therein, we investigated whether directly targeting AT4Rs could counter AD pathogenesis in a well-characterized mouse model of AD. Wild-type and human amyloid precursor protein (APP) transgenic (J20 line) mice (4.5â¯months old) received vehicle or AngIV (~1.3â¯nmol/day, 1â¯month) intracerebroventricularly via osmotic minipumps. AngIV restored short-term memory, spatial learning and memory in APP mice. AngIV normalized hippocampal AT4R levels, increased hippocampal subgranular zone cellular proliferation and dendritic arborization, and reduced oxidative stress. AngIV rescued whisker-evoked neurovascular coupling, endothelial- and smooth muscle cell-mediated cerebral vasodilatory responses, and cerebrovascular nitric oxide bioavailability. AngIV did not alter blood pressure, neuroinflammation or amyloid-ß (Aß) pathology. These preclinical findings identify AT4R as a promising target to counter Aß-related cognitive and cerebrovascular deficits in AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
/
Doença de Alzheimer
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Acoplamento Neurovascular
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Hipocampo
/
Memória
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá