Sex-specific mechanisms of cerebral microvascular BK_Ca dysfunction in a mouse model of Alzheimer's disease.

ABSTRACT:

Introduction

Cerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca²⁺-activated K⁺ channels (BK_Ca) regulate cerebrovascular reactivity and are impaired in AD. BK_Ca activity depends on intracellular Ca²⁺ (Ca²⁺ sparks) and nitro-oxidative post-translational modifications. However, whether these mechanisms underlie BK_Ca impairment in AD remains unknown.

Methods

Cerebral arteries from 5x-FAD and wild-type (WT) littermates were used for molecular biology, electrophysiology, ex vivo, and in vivo experiments.

Results

Arterial BK_Ca activity is reduced in 5x-FAD via sex-dependent mechanisms: in males, there is lower BK_α

SUBMITTER: Silva JF 

PROVIDER: S-EPMC11848394 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature