The interactions of dopamine and oxidative damage in the striatum of patients with neurodegenerative diseases. Issue 2 (4th November 2019)

• Record Type: Journal Article
• Authors: Li, Huifangjie; Yang, Pengfei; Knight, William; Guo, Yingqiu; Perlmutter, Joel S.; Benzinger, Tammie L. S.; Morris, John C.; Xu, Jinbin
• Is Part Of: Journal of neurochemistry. Volume 152:Issue 2(2020)
• Page Start: 235
• Page End: 251
• Publication Date: 2019-11-04
• Subjects: Alzheimer's disease -- dopamine -- Lewy body diseases -- oxidative damage -- striatum; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14898
• Languages: English
• ISSNs: 0022-3042

Abstract

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. Abstract : We hypothesized the following interactions between oxidative damage and dopaminergic biological molecules. One, metabolism of dopamine yields ·OH through the Fenton Reaction and leads to oxidative damage of DNA and RNA molecules. Two, VMAT2 plays a vital anti‐oxidation role. Three, D1R plays a compensatory role against dopamine loss and takes on damage effects in the regulation of BACE1 during these biochemical events. We believe these interactions are involved in the late‐stages of neurodegenerative diseases – resulting in striatal neuron dysfunction.