Blocking β2-adrenergic receptor attenuates acute stress-induced amyloid β peptides production

Abstract

Environmental factors play an important role in the Alzheimer's disease (AD) development and stress may accelerate the progression of AD. β-adrenergic receptors are activated by stress and may influence different aspects of cognitive function. So, it was hypothesized that stress may accelerate the pathological progression of AD by the activation of β 2-adrenergic receptor (β 2-AR). We have investigated the role of acute stress and activation of β 2-AR in amyloid β (Aβ) peptides production in a mouse model of acute restraint stress. Injections of the β 2-AR-selective agonist clenbuterol hydrochloride enhanced the production of acute stress-induced Aβ peptides production; the β 2-AR-selective antagonist ICI 118,551 reduced Aβ peptides production. It is suggested that acute stress induces abnormal activation of β 2-AR which subsequently enhances Aβ peptides (the main neuropathological hallmarks of AD) production possibly resulting in the onset of AD. The findings indicate that new therapeutic strategies designed to blocking β 2-AR might be valuable for the prevention and treatment of AD.