Hypertension Induces Cognitive Impairment and Alterations of Acetylcholine Receptor mRNA Expression in the Hippocampus and Cortex of Mice.

Abstract

Hypertension is a significant risk factor for cognitive decline and dementia, yet the underlying mechanisms linking hypertension to cognitive impairments remain poorly understood. Central acetylcholine (ACh) receptors play a crucial role in the regulation of cognitive function. This study aimed to investigate the effects of hypertension on the mRNA levels of ACh receptors in the hippocampus and medial prefrontal cortex (mPFC). We induced hypertension in mice by continuous Angiotensin II (Ang II) infusion and evaluated cardiovascular parameters as well as cognitive performance using behavioral tests, including the Y-maze, object location task, and Morris water maze. Our findings indicated a significant increase in systolic blood pressure (SBP) and heart weight in Ang II-treated mice without affecting body weight or heart rate. Behavioral assessments revealed notable cognitive deficits characterized by reduced alternation in the Y-maze, impaired object recognition, and increased escape latency in the Morris water maze. Furthermore, quantitative real-time PCR analysis demonstrated reductions in the mRNA levels of muscarinic ACh receptor (Chrm1) and nicotinic ACh receptors (Chrnα4, Chrnα7 and Chrnβ2) in the hippocampus as well as Chrm1, Chrnα5 and Chrnα7 in the mPFC. In addition, correlations were observed between SBP and mRNA levels of labile ACh receptors in mice. Our findings elucidate the critical relationship between hypertension-induced cognitive impairment and the altered mRNA levels of ACh receptors, providing a foundation for future research aimed at restoring cholinergic function and developing therapeutic strategies to mitigate cognitive decline in hypertensive patients.