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Effects of Sirtuin 1 on microglia in spinal cord injury

involvement of Wnt/β-catenin signaling pathway

Lu, Pengfeia,,*; Han, Dongheb,,*; Zhu, Kunmingc; Jin, Meihuab; Mei, Xifanc; Lu, Haixiaa

doi: 10.1097/WNR.0000000000001293
Degeneration and Repair

Because posttraumatic inflammation contributes to the progression of neuron degeneration, attenuating inflammation is important for reducing neural degeneration. Sirtuin 1 (SIRT1) has been shown to play a critical role in the chronic diseases, such as neurodegenerative diseases and aging. However, the role that SIRT1 plays in regulating neuroinflammation in spinal cord injuries (SCIs) remains unclear. In this study, we investigate the effect of SIRT1 on the SCI model and on lipopolysaccharide (LPS)-treated primary microglia using a pharmacological intervention (SRT1720, an agonist of SIRT1). Results showed that SIRT1 levels gradually decreased in spinal cord until the fourth week after SCI, while the level of 8-hydroxy-2’–deoxyguanosine increased. SIRT1 was negatively correlated with the expression of β-catenin following SCI. The administration of SRT1720 significantly improved number of neurons and the Basso, Beattie, and Bresnahan score after SCI. The number of ionizing calcium-binding adaptor molecule 1 (Iba1)-positive microglia, levels of β-catenin and NF-kB p65, and proinflammatory cytokines [tumor necrosis factor alpha and interleukin (IL) 12] decreased significantly after SRT1720 treatment, while IL-10 increased after SCI. Furthermore, both SIRT1 and SRT1720 significantly inhibited β-catenin gene and protein expression; β-catenin transcriptional activity also decreased in a dose-dependent manner following SIRT1 treatment of LPS-treated microglia. These findings suggest that SIRT1 may have a neuroprotective effect by suppressing microglial activation via downregulation of the Wnt/β-catenin signal following SCI.

aInstitute of Neurobiology, Xi’an Jiaotong University Health Science Center, Xi’an

bDepartment of Neurobiology, Key laboratory of Neurodegenerative Disease, Jinzhou Medical University

cDepartment of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

* Dr Pengfei Lu and Dr Donghe Han contributed equally to the writing of this article.

Received 25 March 2019 Accepted 16 June 2019

Correspondence to Haixia Lu, MD, PhD, Institute of Neurobiology, Xi’an Jiaotong University Health Science Center, Xi’an, China, Tel: +86 029 82657064; e-mail:

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins