@article{d2ea1dfd228c4bc6b60d1a308d80b8ab,
title = "The interactions of dopamine and oxidative damage in the striatum of patients with neurodegenerative diseases",
abstract = "The striatum with a number of dopamine containing neurons, receiving projections from the substantia nigra and ventral tegmental area; plays a critical role in neurodegenerative diseases of motor and memory function. Additionally, oxidative damage to nucleic acid may be vital in the development of age-associated neurodegeneration. The metabolism of dopamine is recognized as one of the sources of reactive oxygen species through the Fenton mechanism. The proposed interactions of oxidative insults and dopamine in the striatum during the progression of diseases are the hypotheses of most interest to our study. This study investigated the possibility of significant interactions between these molecules that are involved in the late-stage of Alzheimer's disease (AD), Parkinson disease (PD), Parkinson disease dementia, dementia with Lewy bodies, and controls using ELISA assays, autoradiography, and mRNA in situ hybridization assay. Interestingly, lower DNA/RNA oxidative adducts levels in the caudate and putamen of diseased brains were observed with the exception of an increased DNA oxidative product in the caudate of AD brains. Similar changes were found for dopamine concentration and vesicular monoamine transporter 2 densities. We also found that downstream pre-synaptic dopamine D1 Receptor binding correlated with dopamine loss in Lewy body disease groups, and RNA damage and β-site APP cleaving enzyme 1 in the caudate of AD. This is the first demonstration of region-specific alterations of DNA/RNA oxidative damage which cannot be viewed in isolation, but rather in connection with the interrelationship between different neuronal events; chiefly DNA oxidative adducts and density of vesicular monoamine transporter 2 densities in AD and PD patients. (Figure presented.).",
keywords = "Alzheimer's disease, Lewy body diseases, dopamine, oxidative damage, striatum",
author = "Huifangjie Li and Pengfei Yang and William Knight and Yingqiu Guo and Perlmutter, {Joel S.} and Benzinger, {Tammie L.S.} and Morris, {John C.} and Jinbin Xu",
note = "Funding Information: The authors thank Dr. Nigel Cairns, Ms. Erin E. Franklin, and Mr. Michael Baxter of the Knight Alzheimer Disease Research Center Neuropathology Core at Washington University School of Medicine, for coordination of the tissue preparation and expert technical assistance. Research funded by NIH R01 NS092865, R01 AG052550, R01 NS075321, P01 AG026276, P01 AG03991 and P50 AG05681 as well as the American Parkinson Disease Association (APDA), the Greater St. Louis Chapter of the APDA, the Barnes‐Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease fund), the Oertli Fund and the Riney Foundation. The digital whole slide scanner (Nanozoomer 2‐HT) was supported by a NIH Shared Instrumentation Grant (S10 RR0227552) to Washington University for the Alafi Neuroimaging Laboratory of the Hope Center for Neurological Disorders. The authors have no conflicts of interest and this study was not pre‐registered. All experiments were conducted in compliance with the ARRIVE guidelines. Funding Information: The authors thank Dr. Nigel Cairns, Ms. Erin E. Franklin, and Mr. Michael Baxter of the Knight Alzheimer Disease Research Center Neuropathology Core at Washington University School of Medicine, for coordination of the tissue preparation and expert technical assistance. Research funded by NIH R01 NS092865, R01 AG052550, R01 NS075321, P01 AG026276, P01 AG03991 and P50 AG05681 as well as the American Parkinson Disease Association (APDA), the Greater St. Louis Chapter of the APDA, the Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease fund), the Oertli Fund and the Riney Foundation. The digital whole slide scanner (Nanozoomer 2-HT) was supported by a NIH Shared Instrumentation Grant (S10 RR0227552) to Washington University for the Alafi Neuroimaging Laboratory of the Hope Center for Neurological Disorders. The authors have no conflicts of interest and this study was not pre-registered. All experiments were conducted in compliance with the ARRIVE guidelines. Publisher Copyright: {\textcopyright} 2019 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/jnc.14898",
language = "English",
volume = "152",
pages = "235--251",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
number = "2",
}