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: Xijin Wang, Meihua Wang, Liu Yang, Jie Bai, Zhiqiang Yan, Yuhong Zhang, Zhenguo Liu
• Journal: Neural regeneration research (Neural Regen Res) Vol. 9 Issue 21 Pg. 1917-22 (Nov 01 2014) ISSN: 1673-5374 [Print] India
• PMID: 25558243 (Publication Type: Journal Article)