Amlodipine limits microglia activation and cognitive dysfunction in aged hypertensive mice.

Area of Science:

• Neuroscience
• Pharmacology
• Cardiovascular Medicine

Background:

• Cerebral small vessel disease, linked to stroke and dementia, is associated with systolic blood pressure (SBP) and blood pressure variability.
• Calcium-channel blockers can reduce blood pressure variability, potentially offering neuroprotection.
• The effects of calcium-channel blockers on hypertension-induced neuroinflammation and microglial phenotype are not well understood.

Purpose of the Study:

• To investigate the efficacy of amlodipine in mitigating microglia-associated inflammation.
• To assess the impact of amlodipine on cognitive dysfunction in aged hypertensive mice.
• To explore amlodipine's potential cerebroprotective effects beyond blood pressure reduction.

Main Methods:

• Amlodipine treatment (10 mg/kg/day) in hypertensive BPH/2J mice compared to untreated controls and normotensive BPN/3J mice.
• Blood pressure monitoring via telemetry and tail cuff plethysmography.
• Cognitive function assessment using memory tasks and brain immunohistochemistry for blood-brain barrier integrity and microglial activation (Iba1+CD68+ cells, morphology).

Main Results:

• Amlodipine normalized SBP and decreased blood pressure variability in hypertensive mice.
• Short-term memory impairment in BPH/2J mice was prevented by amlodipine.
• Amlodipine limited blood-brain barrier leakage size and partly reduced microglial inflammatory phenotype (increased Iba1+CD68+ cells, altered cell morphology).

Conclusions:

• Amlodipine attenuated short-term memory deficits in aged hypertensive mice.
• Beyond its antihypertensive effects, amlodipine demonstrates potential cerebroprotection by modulating neuroinflammation and microglial activation.