• Neuroscience · Jun 2018

    Protective Effects of Sulforaphane on Cognitive Impairments and AD-like Lesions in Diabetic Mice are Associated with the Upregulation of Nrf2 Transcription Activity.

    • Die Pu, Yuxing Zhao, Jinliang Chen, Yue Sun, Ankang Lv, Shiyu Zhu, Cheng Luo, Kexiang Zhao, and Qian Xiao.
    • Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, China.
    • Neuroscience. 2018 Jun 15; 381: 35-45.

    AbstractType 2 diabetes mellitus (T2DM)-associated oxidative stress contributes to cognitive deficiencies and Alzheimer's disease (AD). Sulforaphane (SFN) is a pharmacological activator of Nrf2 that provokes Nrf2-mediated intracellular defenses, including antioxidant and anti-inflammatory responses, under oxidative stress (OS) conditions. This study investigated the effects of SFN on DM-related cognitive decline and its potential mechanisms. Morris water maze (MWM) tests showed that SFN (1 mg/kg i.p. for 28 days) mitigated the cognitive decline of db/db mice, a transgenic mouse model of T2DM. Accordingly, immunoblotting and immunohistochemistry analyses showed that SFN decreased the levels of amyloid-β (Aβ) oligomers and Aβ 1-42 plaques as well as phospho-tau at Ser396 and Thr231 in the DM mouse hippocampus. This protective effect of SFN might be due to the activation of Nrf2-regulated antioxidant defense deficiencies in the DM mice, as SFN increased the Nrf2 nuclear accumulation and the downstream expression of the antioxidases HO-1 and NQO1 and reduced the levels of the reactive oxygen/nitrogen species (ROS/RNS) in DM mouse brains. Our results confirm that SFN has potential as a therapeutic agent to protect T2DM patients from cognitive deficiencies and AD-like pathological lesions related to the upregulation of Nrf2-regulated antioxidant defenses.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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