title: Expression of Iron Transporters and Pathological Hallmarks of Parkinson's and Alzheimer's Diseases in the Brain of Young, Adult, and Aged Rats.
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.
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China.
authors: Li-Na
authors: LN
authors: Lu
authors: Laboratory of Neuropharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China. qianzhongming@fudan.edu.cn.
authors: Zhong-Ming
authors: ZM
authors: Qian
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China.
authors: Ka-Chun
authors: KC
authors: Wu
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China.
authors: Wing-Ho
authors: WH
authors: Yung
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China. yake@cuhk.edu.hk.
authors: Ya
authors: Y
authors: Ke
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D064451:Hepcidins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D027682:Cation Transport Proteins; D064451:Hepcidins; D007501:Iron
keywords: Age; Beta-amyloid; Hepcidin; Hyperphosphorylated tau; Iron; Iron uptake and release proteins; α-Synuclein