Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis. Issue 5 (19th December 2018)

• Record Type: Journal Article
• Authors: Ohta, Yasuyuki; Nomura, Emi; Shang, Jingwei; Feng, Tian; Huang, Yong; Liu, Xia; Shi, Xiaowen; Nakano, Yumiko; Hishikawa, Nozomi; Sato, Kota; Takemoto, Mami; Yamashita, Toru; Abe, Koji
• Is Part Of: Journal of neuroscience research. Volume 97:Issue 5(2019)
• Page Start: 607
• Page End: 619
• Publication Date: 2018-12-19
• Subjects: ALS -- edaravone -- in vivo imaging -- nrf2 -- oxidative stress -- SOD1; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24368
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: Oxidative stress is associated with the degeneration of both motor neurons and skeletal muscles in amyotrophic lateral sclerosis (ALS). A free radical scavenger edaravone has been proven as a therapeutic drug for ALS patients, but the neuroprotective mechanism for the oxidative stress of ALS has not been fully investigated. In this study, we investigated oxidative stress in ALS model mice bearing both oxidative stress sensor nuclear erythroid 2‐related factor 2 (Nrf2) and G93A‐human Cu/Zn superoxide dismutase (Nrf2/G93A) treated by edaravone. In vivo Nrf2 imaging analysis showed the accelerated oxidative stress both in spinal motor neurons and lower limb muscles of Nrf2/G93A mice according to disease progression in addition to the enhancement of serum oxidative stress marker dROMS. These were significantly alleviated by edaravone treatment accompanied by clinical improvements (rotarod test). The present study suggests that in vivo optical imaging of Nrf2 is useful for detecting oxidative stress in ALS, and edaravone alleviates the degeneration of both motor neurons and muscles related to oxidative stress in ALS patients. Abstract : In vivo optical imaging of oxidative stress marker Nrf2 in ALS model mice (Nrf2/G93A mice). Note strong Nrf2 signals in the spine and lower limbs of vehicle (V) at the early symptomatic stage with a further emphasis at the late stage, and significant improvement by edaravone (E).