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Expression of Iron Transporters and Pathological Hallmarks of Parkinson’s and Alzheimer’s Diseases in the Brain of Young, Adult, and Aged Rats

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Abstract

Iron accumulates progressively in the brain with age; however, the cause is unknown. We hypothesized that iron accumulation may be associated with the age-induced changes in the expression of iron metabolism proteins in the brain. Here, we systematically investigated iron content and the expression of two major iron importers, transferrin receptor 1 (TfR1) and divalent metal transporter (DMT1), two iron exporters, ferroportin 1 (Fpn1) and ceruloplasmin (CP), and hepcidin, along with the pathological hallmarks of Parkinson’s (PD) and Alzheimer’s diseases (AD) in the brain of young (3 months), adult (12 months), and aged (24 months) rats. We demonstrated that age has a region-specific effect on iron transport proteins along with iron content in the cortex, striatum, hippocampus, and substantia nigra. We also found an age-dependent increase in hyperphosphorylated tau, total beta-amyloid, and neurotoxic oligomeric aggregates in the cortex and hippocampus as well as an increase in α-synuclein and a decrease in tyrosine hydroxylase positive neurons in the substantia nigra. Our findings suggest that the age-dependent increase in brain iron may be partly due to the age-induced increase in DMT1 expression, rather than TfR1 and Fpn1 expression, and also imply that the increased brain iron is associated with expression of the pathological hallmarks of AD and PD.

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Acknowledgments

The studies in our laboratories were supported by the Competitive Earmarked Grants of The Hong Kong Research Grants Council (GRF14106914, GRF14111815), Hong Kong Health and Medical Research Fund (01120146), and the National Natural Science Foundation of China (NSFC) (31330035, 31271132, 31371092, 31571195).

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Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China

    Li-Na Lu, Ka-Chun Wu, Wing-Ho Yung & Ya Ke

  2. Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, People’s Republic of China

    Zhong-Ming Qian

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  1. Li-Na Lu
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Correspondence to Zhong-Ming Qian or Ya Ke.

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Author Contributions

Y.K. and Z.M.Q. conceived, organized, and supervised the study; L.N.L. performed the experiments and K.C.W. helped on iron measurement; Y.K. and W.H.Y. contributed to the analysis and interpretation of data; Y.K. and Z.M.Q. prepared and wrote the manuscript.

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Lu, LN., Qian, ZM., Wu, KC. et al. Expression of Iron Transporters and Pathological Hallmarks of Parkinson’s and Alzheimer’s Diseases in the Brain of Young, Adult, and Aged Rats. Mol Neurobiol 54, 5213–5224 (2017). https://doi.org/10.1007/s12035-016-0067-0

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