Behavioral and Neurochemical Deficits in Aging Rats with Increased Neonatal Iron Intake: Silibinin's Neuroprotection by Maintaining Redox Balance.

Hanqing Chen,Xijin Wang,Liu Yang,Yuhong Zhang,Meihua Wang,Zhenguo Liu,Zhiqiang Yan

doi:10.3389/fnagi.2015.00206

Abstract

Aging is a critical risk factor for Parkinson’s disease. Silibinin, a major flavonoid in Silybum marianum, has been suggested to display neuroprotective properties against various neurodegenerative diseases. In the present study, we observed that neonatal iron (120 μg/g body weight) supplementation resulted in significant abnormality of behavior and depletion of striatal dopamine (DA) in the aging male and female rats while it did not do so in the young male and female rats. No significant change in striatal serotonin content was observed in the aging male and female rats with neonatal supplementation of the same dose of iron. Furthermore, we found that the neonatal iron supplementation resulted in significant increase in malondialdehyde (MDA) and decrease in glutathione (GSH) in the substantia nigra (SN) of the aging male and female rats. No significant change in content of MDA and GSH was observed in the cerebellum of the aging male and female rats with the neonatal iron supplementation. Interestingly, silibinin (25 and 50 mg/kg body weight) treatment significantly and dose-dependently attenuated depletion of striatal DA and improved abnormality of behavior in the aging male and female rats with the neonatal iron supplementation. Moreover, silibinin significantly reduced MDA content and increased GSH content in the SN of the aging male and female rats. Taken together, our results indicate that elevated neonatal iron supplementation may result in neurochemical and behavioral deficits in the male and female rats with aging and silibinin may exert dopaminergic neuroprotection by maintaining redox balance.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by cardinal features, including resting tremor, rigidity, slowness of movement, and postural instability
The neonatal iron intake significantly reduced the content of striatal DA in the aging male and female rats compared with the vehicletreated rats, no significant change in the content of striatal 5HT was observed in the aging male and female rats with the neonatal iron intake in comparison with the vehicle-treated rats (Figures 3C,D)
Aging people gradually exhibit some characteristics of PD, including Lewy bodies, striatal DA decrease, and motor signs, which are similar to those seen in PD

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by cardinal features, including resting tremor, rigidity, slowness of movement, and postural instability. Aging-related neurotoxicity: neuroprotection of silibinin studies have demonstrated that the causes of PD are multifactorial, including aging, exposure to environmental toxins, immune/inflammatory factors, genetic predisposition, and innate characteristics of the nigrostriatal dopaminergic system in the brain (Olanow and Tatton, 1999; Kidd, 2000; Gao et al, 2003; Wang et al, 2005a,b, 2007a,b, 2011; Zhang et al, 2011; Connolly and Lang, 2014). PD is a neurodegenerative disease that is closely associated with aging. Among those factors that have the potential to play a role in idiopathic PD, aging is a critical risk factor for this disease (Yankner et al, 2008; Gureviciene et al, 2009; Hindle, 2010). With further insight into aging and PD, increasing importance is being attached to develop effective therapy strategies for PD through intervening aging-related changes and deficits using aging animals (Dauer and Przedborski, 2003; Connolly and Lang, 2014)

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Conclusion