title: Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake.
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.
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xijin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: Shanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Neurology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
keywords: AK-7; NSFC grants; Parkinson's disease; Sirtuin; aging; corpus striatum; dopamine; iron homeostasis disruption; nerve regeneration; neural regeneration; neurotoxicity