Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice
Journal of Hypertension, vol. 41, pp. 1159–1167
Abstract
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.
Authors 11
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM, School for Cardiovascular Diseases
Department of Neurology, Maastricht University Medical Center
Department of Pathology
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Affiliation as printed
CARIM, School for Cardiovascular Diseases
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Affiliation as printed
Department of Psychiatry and Neuropsychology
MH&NS, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
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Affiliation as printed
Department of Psychiatry and Neuropsychology
MH&NS, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
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Affiliation as printed
CARIM, School for Cardiovascular Diseases
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Affiliation as printed
CARIM, School for Cardiovascular Diseases
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Affiliation as printed
Department of Psychiatry and Neuropsychology
MH&NS, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM, School for Cardiovascular Diseases
Department of Neurology, Maastricht University Medical Center
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Affiliation as printed
CARIM, School for Cardiovascular Diseases
Department of Pathology
IMCAR, Institute for Molecular Cardiology Research, RWTH Aachen, Aachen, Germany
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM, School for Cardiovascular Diseases
Department of Neurology, Maastricht University Medical Center
MH&NS, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
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Sébastien Foulquier corresponding
Affiliation as printed
CARIM, School for Cardiovascular Diseases
Department of Pharmacology-Toxicology, Maastricht University, Maastricht, The Netherlands
MH&NS, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
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