An increasing body of evidence indicates that the activation of indoleamine-2,3-dyoxigenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in Aβ_1–42-neurotoxicity and AD pathogenesis. We have reported for the first time that brain IDO activation is related to Aβ_1–42 exposure in young mice. Because aging is characterized by a brain dyshomeostasis and because it remains the most dominant risk factor for AD, the purpose of this study was to determine whether aging is associated with a higher sensitivity to behavioural and neurochemical alterations elicited by an intracerebroventricular (i.c.v.) injection of Aβ_1–42 (400 pmol/mice), and whether KYN pathway is involved in these effects. We confirmed that aged mice displayed higher cognitive deficit in the object recognition test and higher anxiety-like behaviour in the elevated plus-maze and open field tests after the Aβ_1–42 administration. Aged mice also responded to Aβ_1–42 with a higher deficiency of brain-derived neurotrophic factor, glutathione levels and total radical-trapping antioxidant capacity, a higher IDO activity, and a higher KYN and KYN/tryptophan ratio in the prefrontal cortex and hippocampus. These effects of Aβ_1–42 were associated with a higher proinflammatory status, as measured by higher levels of interleukin-6, lower levels of interleukin-10 and higher expression of glial fibrillary acidic protein (GFAP) and allograft inflammatory factor 1 (Iba1) in the brain of aged mice. These results represent primary evidence suggesting that age-associated inflammatory signature and down-regulation of neuroprotectants in the brain render aged mice more vulnerable to Aβ_1–42-induced memory loss, anxiety symptoms and KYN pathway dysregulation.

越来越多的证据体表示吲哚胺-2,3- dyoxigenase（IDO）的激活，第一和速率限制在犬尿氨酸（KYN）途径酶，参与Aβ _1-42 -neurotoxicity和AD发病。我们首次报道大脑IDO的激活与幼鼠的_Aβ1–42暴露有关。由于衰老的特点是脑部动态失调，并且它仍然是AD的最主要危险因素，因此本研究的目的是确定衰老是否与脑室内（icv）注射脑室内注入引起的行为和神经化学变化的敏感性更高有关。 Aβ _1-42（400 pmol /小鼠），以及这些效应是否涉及KYN途径。我们证实，在_Aβ1–42给药后，老年小鼠在物体识别测试中显示出更高的认知缺陷，在升高的迷宫和开放视野测试中表现出更高的焦虑样行为。老年小鼠还对_Aβ1–42做出反应，脑源性神经营养因子，谷胱甘肽水平和总自由基捕获抗氧化能力的缺乏更高，IDO活性更高，前额叶皮层和海马中的KYN和KYN /色氨酸比更高。 。_Aβ1–42的这些作用老年小鼠的大脑中，白细胞介素6的水平较高，白细胞介素10的水平较低以及神经胶质纤维酸性蛋白（GFAP）和同种异体移植炎症因子1（Iba1）的表达水平较高，因此它们与较高的促炎状态相关。这些结果代表了主要证据，表明与年龄相关的炎症反应和大脑中神经保护剂的下调使老年小鼠更易受_Aβ1–42诱导的记忆力丧失，焦虑症状和KYN通路失调的影响。