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Increased iron levels correlate with the selective nigral dopaminergic neuron degeneration in Parkinson’s disease

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The staging of Lewy-related pathology in sporadic Parkinson’s disease (PD) reveals that many brain nuclei are affected in PD during different stages, except the ventral tegmental area (VTA), which is close related to the substantia nigra (SN) and enriched in dopamine (DA) neurons. Why DA neurons are selectively degenerated in the SN of PD is far from known. In the present study, we observed that the number of tyrosine hydroxylase immunoreactive neurons decreased and iron-staining positive cells increased in the SN, but not in the VTA, in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated PD mice. Increased expression of divalent metal transporter 1 and decreased expression of ferroportin 1 might associate with this increased nigral iron levels. Lipofuscin granular aggregations and upregulation of alpha-synuclein (α-synuclein) were also observed only in the SN. These results suggest that increased iron levels associate with the selective degeneration of DA neurons in the SN. The intracellular regulation mechanisms for the iron transporters may be different in the SN and VTA under the same conditions. Moreover, the lipofuscin granular aggregations and upregulation of α-synuclein were also involved in the selective degeneration of dopaminergic neurons in the SN.

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Acknowledgments

This study was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2006CB500704), the National Foundation of Natural Science of China (30930036, 30870858) and the Natural Science Fund of Shandong Province for Distinguished Young Scholars (JQ200807).

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Authors and Affiliations

  1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Medical College of Qingdao University, Qingdao, 266071, China

    Zhanyun Lv, Hong Jiang, Huamin Xu, Ning Song & Junxia Xie

  2. Department of Physiology, State Key Disciplines: Physiology in Incubation, Medical College of Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, China

    Zhanyun Lv, Hong Jiang, Huamin Xu, Ning Song & Junxia Xie

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  1. Zhanyun Lv
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  2. Hong Jiang
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Correspondence to Junxia Xie.

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Lv, Z., Jiang, H., Xu, H. et al. Increased iron levels correlate with the selective nigral dopaminergic neuron degeneration in Parkinson’s disease. J Neural Transm 118, 361–369 (2011). https://doi.org/10.1007/s00702-010-0434-3

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  • DOI: https://doi.org/10.1007/s00702-010-0434-3

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