Julissa Massanett Aparicio1, Yanxun Xu2,3, Yuliang Li2, Carlo Colantuoni4,5, Raha Dastgheyb4, Dionna W Williams6,7, Eugene L Asahchop8, Jacqueline M McMillian9,10, Christopher Power10,8,11, Esther Fujiwara11,12, M John Gill9,10, Leah H Rubin4,13,14. 1. Midwestern University, Glendale, Arizona. 2. Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore. 3. Division of Biostatistics and Bioinformatics at The Sidney Kimmel Comprehensive Cancer Center. 4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore. 5. Institute for Genome Sciences, University of Maryland, Baltimore. 6. Department of Molecular and Comparative Pathobiology. 7. Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 8. Department of Medicine. 9. Cumming School of Medicine, University of Calgary. 10. Southern Alberta Clinic, Calgary. 11. Neuroscience and Mental Health Institute. 12. Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada. 13. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine. 14. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Abstract
OBJECTIVE: Cognitive impairment remains common in people with HIV (PWH) on antiretroviral therapy (ART). The clinical presentation and severity are highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA (miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons. We examined plasma miRNA expression changes in relation to domain-specific and global cognitive function in PWH. DESIGN: Cross-sectional observational study. METHODS: Thirty-three PWH receiving care at the Southern Alberta Clinic, Canada completed neuropsychological (NP) testing and blood draw. Plasma miRNA extraction was followed by array hybridization. Random forest analysis was used to identify the top 10 miRNAs upregulated and downregulated in relation to cognition. RESULTS: Few miRNAs were identified across cognitive domains; however, when evident a miRNA was only associated with two or three domains. Notably, miR-127-3p was related to learning/memory and miR-485-5p to motor function, miRNAs previously identified in CSF or plasma in Alzheimer's and Parkinson's, respectively. Using miRNET 2.0, a software-platform for understanding the biological relevance of the miRNA-targets (genes) relating to cognition through a network-based approach, we identified genes involved in signaling, cell cycle, and transcription relating to executive function, learning/memory, and language. CONCLUSION: Findings support the idea that evaluating miRNA expression (or any molecular measure) in the context of global NP function might exclude miRNAs that could be important contributors to the domain-specific mechanisms leading to the variable neuropsychiatric outcomes seen in PWH.
OBJECTIVE: Cognitive impairment remains common in people with HIV (PWH) on antiretroviral therapy (ART). The clinical presentation and severity are highly variable in PWH suggesting that the pathophysiological mechanisms of cognitive complications are likely complex and multifactorial. MicroRNA (miRNA) expression changes may be linked to cognition as they are gene regulators involved in immune and stress responses as well as the development, plasticity, and differentiation of neurons. We examined plasma miRNA expression changes in relation to domain-specific and global cognitive function in PWH. DESIGN: Cross-sectional observational study. METHODS: Thirty-three PWH receiving care at the Southern Alberta Clinic, Canada completed neuropsychological (NP) testing and blood draw. Plasma miRNA extraction was followed by array hybridization. Random forest analysis was used to identify the top 10 miRNAs upregulated and downregulated in relation to cognition. RESULTS: Few miRNAs were identified across cognitive domains; however, when evident a miRNA was only associated with two or three domains. Notably, miR-127-3p was related to learning/memory and miR-485-5p to motor function, miRNAs previously identified in CSF or plasma in Alzheimer's and Parkinson's, respectively. Using miRNET 2.0, a software-platform for understanding the biological relevance of the miRNA-targets (genes) relating to cognition through a network-based approach, we identified genes involved in signaling, cell cycle, and transcription relating to executive function, learning/memory, and language. CONCLUSION: Findings support the idea that evaluating miRNA expression (or any molecular measure) in the context of global NP function might exclude miRNAs that could be important contributors to the domain-specific mechanisms leading to the variable neuropsychiatric outcomes seen in PWH.
Authors: Kasandra Burgos; Ivana Malenica; Raghu Metpally; Amanda Courtright; Benjamin Rakela; Thomas Beach; Holly Shill; Charles Adler; Marwan Sabbagh; Stephen Villa; Waibhav Tembe; David Craig; Kendall Van Keuren-Jensen Journal: PLoS One Date: 2014-05-05 Impact factor: 3.240
Authors: Matthias Hackl; Stefan Brunner; Klaus Fortschegger; Carina Schreiner; Lucia Micutkova; Christoph Mück; Gerhard T Laschober; Günter Lepperdinger; Natalie Sampson; Peter Berger; Dietmar Herndler-Brandstetter; Matthias Wieser; Harald Kühnel; Alois Strasser; Mark Rinnerthaler; Michael Breitenbach; Michael Mildner; Leopold Eckhart; Erwin Tschachler; Andrea Trost; Johann W Bauer; Christine Papak; Zlatko Trajanoski; Marcel Scheideler; Regina Grillari-Voglauer; Beatrix Grubeck-Loebenstein; Pidder Jansen-Dürr; Johannes Grillari Journal: Aging Cell Date: 2010-01-18 Impact factor: 9.304