Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice
| العنوان: | Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice |
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| المؤلفون: | Danielle Kerkhofs, Robin Helgers, Denise Hermes, Hellen P.J. Steinbusch, Helma Van Essen, Peter Leenders, Jos Prickaerts, Julie Staals, Erik A. Biessen, Robert J. Van Oostenbrugge, Sébastien Foulquier |
| المصدر: | Journal of Hypertension. 41(7):1159-1167 |
| بيانات النشر: | LIPPINCOTT WILLIAMS & WILKINS, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Male, Physiology, Amlodipine/pharmacology, Antihypertensive Agents/pharmacology, Mice, Hypertension/complications, Calcium Channel Blockers/therapeutic use, Neuroinflammatory Diseases, Internal Medicine, Humans, Animals, Calcium, Dementia, Microglia, Cardiology and Cardiovascular Medicine, Prostatic Hyperplasia/drug therapy, Blood Pressure/physiology |
| الوصف: | BACKGROUND: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.METHODS: Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).RESULTS: Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.CONCLUSION: Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation. |
| اللغة: | English |
| تدمد: | 1473-5598 0263-6352 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::218cccbd589fa021577764eeaded438a https://doi.org/10.1097/HJH.0000000000003445 |
| رقم الأكسشن: | edsair.doi.dedup.....218cccbd589fa021577764eeaded438a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14735598 02636352 |
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