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...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 signiifcant 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 signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.展开更多
基金supported by the National Natural Science Foundation of China,No.81171204,81171203,30772280,81200871,and 81200921a grant from the Project of Shanghai Municipal Education Commission of China,No.14YZ046+2 种基金a grant from the Project of Shanghai Municipal Health and Family Planning Commission of China,No.20134049a grant from the Project of Shanghai Jiao Tong University of China,No.YG2013MS22a grant from the Projects of Shanghai Committee of Science and Technology of China,No.11nm0503300 and 12XD1403800
文摘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 signiifcant 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 signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.
