Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, 71122 Foggia, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli 20, 71122 Foggia, Italy.
Eur J Pharmacol. 2017 Dec 15;817:22-29. doi: 10.1016/j.ejphar.2017.08.031. Epub 2017 Aug 24.
Chronic stress is considered a widely accepted risk factor for the development of neuropsychiatric and neurological disorders. Indeed, high cortisol levels, and, thus, hypothalamic pituitary adrenal (HPA)-axis dysregulation, have been indicated as the most frequent alteration in patients affected by depression, as well as by Alzheimer's disease (AD). Furthermore, depressive state has been pointed as an early manifestation of AD, advocating an overlap between these neuropathological events. We have previously demonstrated that central soluble beta amyloid 1-42 (Aβ) administration peptide induces a depressive like-behavior in rats, with altered HPA axis activation, reduced cortical serotonin and neurotrophin levels. The crucial role of Aβ in stress response is becoming more and more evident, indeed many reports indicate that its release is increased in stressful conditions and stress-based paradigm. Furthermore, it has been reported that stress controls Aβ production and/or clearance. Chronic stress is responsible of inducing neuroinflammation processes and reduced serotoninergic tone, both pathophysiological mechanisms proposed in the association of depression with another chronic disease, such as diabetes. Likewise, AD has also been indicated as type 3 diabetes, considering the large body of literature that suggests common biological bases. Thus, the main aim of the present review is to evaluate the most recent literature findings in humans and animal models in regard to the role of Aβ in stress response and in relation to the biological substrates and pathological pathways common to AD and comorbid diseases, such as depression and diabetes.
慢性应激被认为是神经精神和神经退行性疾病发展的一个广泛认可的风险因素。事实上，高皮质醇水平，以及由此导致的下丘脑-垂体-肾上腺（HPA）轴失调，已被表明是抑郁症和阿尔茨海默病（AD）患者最常见的改变。此外，抑郁状态被认为是 AD 的早期表现，这表明这些神经病理事件之间存在重叠。我们之前已经证明，中枢可溶性β淀粉样蛋白 1-42（Aβ）肽给药会在大鼠中诱导出类似抑郁的行为，同时伴有 HPA 轴激活、皮质层 5-羟色胺和神经营养因子水平降低。Aβ 在应激反应中的关键作用变得越来越明显，事实上，许多报道表明，在应激条件和应激模型下，Aβ 的释放会增加。此外，有报道称，应激控制 Aβ 的产生和/或清除。慢性应激会导致神经炎症过程和 5-羟色胺能神经递质减少，这两种病理生理机制都被认为与抑郁症和另一种慢性疾病（如糖尿病）有关。同样，AD 也被认为是 3 型糖尿病，因为大量文献表明存在共同的生物学基础。因此，本综述的主要目的是评估人类和动物模型中关于 Aβ 在应激反应中的作用以及与 AD 和共病（如抑郁症和糖尿病）的共同生物学基础和病理途径的最新文献发现。
