Journal of Alzheimers Disease & Parkinsonism
Open Access

Identifying Neuronal Signatures of Oxidative Stress via Small Extracellular Vesicle miRNA Profiling

Kumudu Subasinghe, Courtney Hall, Isabelle Gorham, Rucha Trivedi, Amalendu Ranjan, Jamie Y. Choe, Megan Rowe, Jamboor K. Vishwanatha, Robert Barber, Harlan Jones and Nicole Phillips^*

¹Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, USA

²Department of Family Health (TCOM); University of North Texas Health Science Center, Fort Worth, USA

³Department of Translational Medicine, University of North Texas Health Science Center, Fort Worth, USA

⁴Department of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, USA

⁵Department of Health Disparities, University of North Texas Health Science Center, Fort Worth, USA

⁶Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA

Received Date: Sep 09, 2024 / Published Date: Oct 09, 2024

Citation: Subasinghe K, Hall C, Gorham I, Trivedi R, Ranjan A, et al. (2024). Identifying Neuronal Signatures of Oxidative Stress via Small Extracellular Vesicle miRNA Profiling. J Alzheimers Dis Parkinsonism 14: 618

Copyright: © 2024 Amine JM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

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Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that affects the aging population due to both environmental exposures and genetic risk factors. It is proposed that cell damage caused by oxidative stress contributes to the pathogenesis of AD. Evidence suggests that early alterations in AD-affected brains can propagate to local and distal cells through neuronal release of Extracellular Vesicles (EVs) which can cross the blood-brain barrier. These circulating EVs thus represent an easily accessible derivative of the brain in living humans. Exosomes, a type of small extracellular vessicle, contain various bioactive cargo including small, non-coding Ribonucleic Acids (RNAs) known as microRNAs (miRNA) that act as strong regulators of gene expression and can elicit effects in target cells. Here we aimed to experimentally identify candidate miRNAs that neuronal cells release in Small EVs (sEVs), such as exosomes, when under oxidative stress.

Method: Sohin-Keeler Neuroblastoma Cell line, Medium Culture (SK-N-MC) cells were treated with Hydrogen Peroxide (H₂O₂) to induce oxidative stress and miRNAs from both the SK-N-MC cells themselves as well as those contained in released sEVs were extracted and sequenced. Differentially expressed miRNAs were analyzed using Qiagen’s RNA-seq analysis portal and ingenuity pathway analysis.

Results: We identified a miRNA profile indicative of H₂O₂ exposure in neuronal sEVs–six miRNAs exhibited overrepresentation and two miRNAs exhibited underrepresentation with increasing H₂O₂ treatment. Differentially expressed miRNAs were assayed with quantitative Polymerase Chain Reaction (PCR) in an independent experimental replication.

Conclusion: These eight miRNAs are involved in many cellular processes, including regulation of Nuclear Factor Kappa B (NF-κB) complex associated genes and their related cellular responses. Their presence in sEVs from neurons may indicate the presence of oxidative stress and subsequently alter local and/or systemic responses.

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