Effects of Combined Anti-Hypertensive and Statin Treatment on Memory, Fear Extinction, Adult Neurogenesis, and Angiogenesis in Adult and Middle-Aged Mice.
Cells
; 10(7)2021 07 14.
Article
em En
| MEDLINE
| ID: mdl-34359946
ABSTRACT
Hyperlipidemia and hypertension are modifiable risk factors for cognitive decline. About 25% of adults over age 65 use both antihypertensives (AHTs) and statins to treat these conditions. Recent research in humans suggests that their combined use may delay or prevent dementia onset. However, it is not clear whether and how combination treatment may benefit brain function. To begin to address this question, we examined effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and Captopril, an angiotensin-converting enzyme inhibitor (ACEI), administration on memory function, anxiety-like behavior, adult hippocampal neurogenesis and angiogenesis in adult and middle-aged male C57Bl/6J mice. In adult mice (3-months-old) combination (combo) treatment, as well as administration of each compound individually, for six weeks, accelerated memory extinction in contextual fear conditioning. However, pattern separation in the touchscreen-based location discrimination test, a behavior linked to adult hippocampal neurogenesis, was unchanged. In addition, dentate gyrus (DG) neurogenesis and vascularization were unaffected. In middle-aged mice (10-months-old) combo treatment had no effect on spatial memory in the Morris water maze, but did reduce anxiety in the open field test. A potential underlying mechanism may be the modest increase in new hippocampal neurons (~20%) in the combo as compared to the control group. DG vascularization was not altered. Overall, our findings suggest that statin and anti-hypertensive treatment may serve as a potential pharmacotherapeutic approach for anxiety, in particular for post-traumatic stress disorder (PTSD) patients who have impairments in extinction of aversive memories.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores Etários
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Neurogênese
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Medo
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Memória
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Anti-Hipertensivos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article