The First Clinic Medical College, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
Queen Mary Institute, School of Medicine, Nanchang University, Nanchang, Jiangxi, 330006, China.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):1016-1022. doi: 10.1016/j.bbrc.2018.05.101. Epub 2018 May 18.
The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ treatment. We found that Aβ microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ-treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.
淀粉样蛋白-β (Aβ) 的积累和氧化应激损伤被认为是阿尔茨海默病 (AD) 的早期特征。可卡因和安非他命调节转录物 (CART) 肽可能在神经元中发挥抗氧化作用。本研究旨在探讨 CART 肽在 AD 大鼠模型中的潜在抗氧化机制。我们将 Aβ（2μl/4μg/半脑）微注射到大鼠海马体中，建立 AD 大鼠模型。在 Aβ 处理前连续 5 天，将 CART 肽（1μl/0.02μg/半脑）预先微注射到大鼠海马体中。我们发现 Aβ 微注射导致大鼠海马体中内源性 CART 水平降低。CART 预处理改善了 AD 大鼠的空间记忆和运动能力。CART 肽降低了 Aβ 和 Aβ 产生相关酶 BACE1 的水平。此外，CART 肽减轻了氧化应激损伤，具体表现为 Aβ 处理大鼠海马体中 MDA 增加，T-SOD、GSH 和 ATP 水平降低，这可能与 Nrf2/HO-1 信号通路的激活有关。此外，CART 肽降低了大鼠海马体中 Bax、caspase-9 和 caspase-3 水平的升高和 Bcl-2 水平的升高，表明神经元凋亡减少。我们的研究结果表明，CART 肽可作为 AD 早期治疗的抗氧化剂。
