Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, PR China.
Brain Res. 2010 Mar 4;1317:305-10. doi: 10.1016/j.brainres.2009.12.087. Epub 2010 Jan 6.
Environmental factors play an important role in the Alzheimer's disease (AD) development and stress may accelerate the progression of AD. Beta-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 beta(2)-adrenergic receptor (beta(2)-AR). We have investigated the role of acute stress and activation of beta(2)-AR in amyloid beta (Abeta) peptides production in a mouse model of acute restraint stress. Injections of the beta(2)-AR-selective agonist clenbuterol hydrochloride enhanced the production of acute stress-induced Abeta peptides production; the beta(2)-AR-selective antagonist ICI 118,551 reduced Abeta peptides production. It is suggested that acute stress induces abnormal activation of beta(2)-AR which subsequently enhances Abeta 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 beta(2)-AR might be valuable for the prevention and treatment of AD.
环境因素在阿尔茨海默病（AD）的发展中起着重要作用，压力可能会加速 AD 的进展。β-肾上腺素能受体被压力激活，可能会影响认知功能的不同方面。因此，有人假设压力可能通过激活β2-肾上腺素能受体（β2-AR）加速 AD 的病理进展。我们已经在急性束缚应激的小鼠模型中研究了急性应激和β2-AR 激活在淀粉样β（Abeta）肽产生中的作用。β2-AR 选择性激动剂盐酸克仑特罗的注射增强了急性应激诱导的 Abeta 肽产生；β2-AR 选择性拮抗剂 ICI 118,551 减少了 Abeta 肽的产生。这表明急性应激诱导β2-AR 的异常激活，随后增强 Abeta 肽（AD 的主要神经病理学标志）的产生，可能导致 AD 的发生。研究结果表明，旨在阻断β2-AR 的新治疗策略可能对 AD 的预防和治疗有价值。
