Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (21): 1917-1922.doi: 10.4103/1673-5374.145361

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Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake

Xijin Wang 1, Meihua Wang 1, Liu Yang 1, Jie Bai 1, Zhiqiang Yan 2, Yuhong Zhang 3, Zhenguo Liu 1   

  1. 1 Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2 Shanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai, China
    3 Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
  • Received:2014-09-28 Online:2014-11-15 Published:2014-11-15
  • Contact: Zhenguo Liu, M.D., Ph.D., Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China, zhenguoliu2004@aliyun.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81171204, 81171203, 30772280, 81200871, and 81200921; a grant from the Project of Shanghai Municipal Education Commission of China, No. 14YZ046; a grant from the Project of Shanghai Municipal Health and Family Planning Commission of China, No. 20134049; a grant from the Project of Shanghai Jiao Tong University of China, No. YG2013MS22; and a grant from the Projects of Shanghai Committee of Science and Technology of China, No. 11nm0503300 and 12XD1403800.

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Abstract:

Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 µg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 µg/side per day), striatal dopamine depletion was significantly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental findings suggest that increased neonatal iron intake may result in Parkinson’s disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

Key words: nerve regeneration, Parkinson’s disease, iron homeostasis disruption, aging, dopamine, corpus striatum, neurotoxicity, Sirtuin, AK-7, NSFC grants, neural regeneration