CDDO-Im exerts antidepressant-like effects via the Nrf2/ARE pathway in a rat model of post-stroke depression.

Xiaoli Hou, Huanhuan Liu, Yukun Ping, Feng Zhang, Lingyun Zhi, Xinhui Jiang, Fuping Zhang, Cai Song, Zhaohui Zhang, Jinggui Song

Brain research bulletin 2021 Aug

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Increasing evidence suggests that oxidative damage and neuroinflammation play a critical role in the pathogenesis of post-stroke depression (PSD). These pathologic processes are tightly regulated by the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. The synthetic triterpenoid, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im), is a potent Nrf2 activator. This study investigated whether CDDO-Im exhibited antidepressant-like activity and elucidated its protective mechanisms in a rat model of PSD, which was produced by middle cerebral artery occlusion (MCAO) followed by 28 days of chronic unpredictable mild stress (CUMS) in conjunction with solitary housing. The results demonstrated that CDDO-Im treatment markedly improved the depressive-like behaviors and reduced neuronal cell loss in the hippocampus, through decreasing the malondialdehyde (MDA) content (indicative of lipid peroxidation), superoxide dismutase (SOD), NF-kB activation, interleukin-6 (IL-6) and interleukin-1b (IL-1β) in PSD rats. CDDO-Im treatment alleviated the oxidative stress and inflammatory response in PSD rats by promoting Nrf2 nuclear import and increasing the protein levels of Nrf2 downstream target genes, including heme oxygenase-1(HOMX1) and, quinone oxidoreductase-1(NQO1).These findings suggested that CDDO-Im treatment exhibited antidepressant-like effects and protected PSD rats from oxidative and inflammatory injury via the Nrf2/ARE pathway. Therefore, CDDO-Im treatment is worthy of further study. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Xiaoli Hou, Huanhuan Liu, Yukun Ping, Feng Zhang, Lingyun Zhi, Xinhui Jiang, Fuping Zhang, Cai Song, Zhaohui Zhang, Jinggui Song. CDDO-Im exerts antidepressant-like effects via the Nrf2/ARE pathway in a rat model of post-stroke depression. Brain research bulletin. 2021 Aug;173:74-81