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JOURNAL ARTICLE
Hubert Monnerie, Micah Romer, Lindsay M Roth, Caela Long, John S Millar, Kelly L Jordan-Sciutto, Judith B Grinspan
Combined antiretroviral therapy (cART) has greatly decreased mortality and morbidity among persons with HIV; however, neurologic impairments remain prevalent, in particular HIV-associated neurocognitive disorders (HANDs). White matter damage persists in cART-treated persons with HIV and may contribute to neurocognitive dysfunction as the lipid-rich myelin membrane of oligodendrocytes is essential for efficient nerve conduction. Because of the importance of lipids to proper myelination, we examined the regulation of lipid synthesis in oligodendrocyte cultures exposed to the integrase strand transfer inhibitor elvitegravir (EVG), which is administered to persons with HIV as part of their initial regimen...
2023: Frontiers in Molecular Neuroscience
#2
REVIEW
Lindsay K Festa, Judith B Grinspan, Kelly L Jordan-Sciutto
Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become increasingly apparent that injury to cells within the OL lineage plays a central role in neurodegeneration. In this review, we focus primarily on three degenerative disorders in which white matter loss is well documented: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We discuss clinical data implicating white matter injury as a key feature of these disorders, as well as shared and divergent phenotypes between them...
December 4, 2023: Trends in Neurosciences
#3
JOURNAL ARTICLE
Lily P See, Puttipong Sripinun, Wennan Lu, Jiaqi Li, Naela Alboloushi, Elena Alvarez-Periel, Su-Min Lee, Bekir Karabucak, Steven Wang, Kelly L Jordan Sciutto, Katherine N Theken, Claire H Mitchell
An enhanced understanding of neurotransmitter systems contributing to pain transmission aids in drug development, while the identification of biological variables like age and sex helps in the development of personalized pain management and effective clinical trial design. This study identified enhanced expression of purinergic signaling components specifically in painful inflammation, with levels increased more in women as compared to men. Inflammatory dental pain is common and potentially debilitating; as inflammation of the dental pulp can occur with or without pain, it provides a powerful model to examine distinct pain pathways in humans...
November 11, 2023: Journal of Pain
#4
JOURNAL ARTICLE
Edward F Kreider, Yohaniz Ortega-Burgos, Jeriel Dumeng-Rodriguez, James Gesualdi, Caroline O'Brien, Danny Bracy, Jeanene Johnson, Jacqui Bowman, David Metzger, C Jessica Dine, Kevin Favor, Kelly L Jordan-Sciutto, Florence Momplaisir
BACKGROUND: Demographic diversity is not represented in the HIV/AIDS workforce. Engagement of underrepresented trainees as early as high school may address this disparity. METHODS: We established the Penn Center for AIDS Research (CFAR) Scholars Program, a mentored research experience for underrepresented minority (URM) trainees spanning educational stages from high school to medical school. The program provides participants with tailored educational programming, professional skill building, and mentored research experiences...
October 1, 2023: Journal of Acquired Immune Deficiency Syndromes: JAIDS
#5
MULTICENTER STUDY
Manya Magnus, Lorena Segarra, Brandi Robinson, Kim Blankenship, Amy Corneli, Musie Ghebremichael, Nathan Irvin, Roger McIntosh, Kevin E Favor, Kelly L Jordan-Sciutto, Judy Kimberly, Nicolas Sluis-Cremer, John R Koethe, Alana Newell, Christine Wood, Aadia Rana, Jamila K Stockman, John Sauceda, Carina Marquez, Benjamin H Chi, E Roberto Orellana, Anthony Wutoh, Lisa Bowleg, Alan E Greenberg
BACKGROUND: The Centers for AIDS Research Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) aims to establish programs to develop pathways for successful careers in HIV science among scholars from underrepresented racial and ethnic populations. This article describes cross-site evaluation outcomes during the first 18 months (July 2021-December 2022) across 15 programs. METHODS: The aims of the evaluation were to characterize participants, describe feasibility, challenges, and successes of the programs and provide a basis for the generalizability of best practices to Diversity, Equity, and Inclusion (DEI) programs in the United States...
October 1, 2023: Journal of Acquired Immune Deficiency Syndromes: JAIDS
#6
JOURNAL ARTICLE
Alan E Greenberg, Anthony Wutoh, Lisa Bowleg, Brandi Robinson, Manya Magnus, Lorena Segarra, Patti Simon, Anthony Wutoh, Kim Blankenship, Mark Burke, Nwora Lance Okeke, Amy Corneli, Sophia Hussen, Rhonda C Holliday, Andrea Ciaranello, Musie Ghebremichael, Jessica Haberer, Risha Irvin, Nathan Irvin, Denis G Antoine, Zhibin Chen, Florence Momplaisir, Kelly Jordan-Sciutto, Kaku So-Armah, Caroline Kuo, Timothy Flanigan, Martha Sanchez, Alan D Levine, Nicolas Sluis-Cremer, John R Koethe, Chandravanu Dash, Fred A Pereira, Andrew P Rice, Alana Newell, Jagadīśadevaśrī Dācus, Christine Wood, Latesha Elopre, Aadia Rana, Eileen Pitpitan, Jamila K Stockman, John Sauceda, Carina Marquez, Seronda Robinson, Benjamin H Chi, Jennifer Balkus, Karina Walters, Anya Lewin, Annalise Schoonmaker, Elaine Wong, Eric Refsland
BACKGROUND: There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. METHODS: To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI)...
October 1, 2023: Journal of Acquired Immune Deficiency Syndromes: JAIDS
#7
REVIEW
Jennifer L McGuire, Judith B Grinspan, Kelly L Jordan-Sciutto
PURPOSE OF REVIEW: : Behaviorally acquired (non-perinatal) HIV infection during adolescence and young adulthood occurs in the midst of key brain developmental processes such as frontal lobe neuronal pruning and myelination of white matter, but we know little about the effects of new infection and therapy on the developing brain. RECENT FINDINGS: Adolescents and young adults account for a disproportionately high fraction of new HIV infections each year. Limited data exist regarding neurocognitive performance in this age group, but suggest impairment is at least as prevalent as in older adults, despite lower viremia, higher CD4 + T cell counts, and shorter durations of infection in adolescents/young adults...
February 21, 2023: Current HIV/AIDS Reports
#8
JOURNAL ARTICLE
Lindsay K Festa, Abigail E Clyde, Caela C Long, Lindsay M Roth, Judith B Grinspan, Kelly L Jordan-Sciutto
White matter deficits are a common neuropathologic finding in neurologic disorders, including HIV-associated neurocognitive disorders (HAND). In HAND, the persistence of white matter alterations despite suppressive antiretroviral (ARV) therapy suggests that ARVs may be directly contributing to these impairments. Here, we report that a frontline ARV, bictegravir (BIC), significantly attenuates remyelination following cuprizone-mediated demyelination, a model that recapitulates acute demyelination, but has no impact on already formed mature myelin...
January 31, 2023: Journal of Neurochemistry
#9
EDITORIAL
Anthony J Filiano, Kelly L Jordan-Sciutto
No abstract text is available yet for this article.
January 4, 2023: Current Opinion in Neurobiology
#10
JOURNAL ARTICLE
Aidan T Pezacki, Carson D Matier, Xingxing Gu, Eric Kummelstedt, Sarah E Bond, Laura Torrente, Kelly L Jordan-Sciutto, Gina M DeNicola, Timothy A Su, Donita C Brady, Christopher J Chang
Copper is an essential metal nutrient for life that often relies on redox cycling between Cu(I) and Cu(II) oxidation states to fulfill its physiological roles, but alterations in cellular redox status can lead to imbalances in copper homeostasis that contribute to cancer and other metalloplasias with metal-dependent disease vulnerabilities. Copper-responsive fluorescent probes offer powerful tools to study labile copper pools, but most of these reagents target Cu(I), with limited methods for monitoring Cu(II) owing to its potent fluorescence quenching properties...
October 25, 2022: Proceedings of the National Academy of Sciences of the United States of America
#11
JOURNAL ARTICLE
Claudia Lopez Lloreda, Sarah Chowdhury, Shivesh Ghura, Elena Alvarez-Periel, Kelly Jordan-Sciutto
Neurologic deficits associated with human immunodeficiency virus (HIV) infection impact about 50% of persons with HIV (PWH). These disorders, termed HIV-associated neurocognitive disorders (HAND), possess neuropathologic similarities to Alzheimer's disease (AD), including intra- and extracellular amyloid-beta (Aβ) peptide aggregates. Aβ peptide is produced through cleavage of the amyloid precursor protein (APP) by the beta secretase BACE1. However, this is precluded by cleavage of APP by the non-amyloidogenic alpha secretase, ADAM10...
September 22, 2022: Cells
#12
JOURNAL ARTICLE
Alyson S Smith, Soneela Ankam, Chen Farhy, Lorenzo Fiengo, Ranor C B Basa, Kara L Gordon, Charles T Martin, Alexey V Terskikh, Kelly L Jordan-Sciutto, Jeffrey H Price, Patrick M McDonough
INTRODUCTION: Despite viral suppression due to combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) continue to affect half of people with HIV, suggesting that certain antiretrovirals (ARVs) may contribute to HAND. METHODS: We examined the effects of nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG) on viability, structure, and function of glutamatergic neurons (a subtype of CNS neuron involved in cognition) derived from human induced pluripotent stem cells (hiPSC-neurons), and primary human neural precursor cells (hNPCs), which are responsible for neurogenesis...
February 7, 2022: Journal of Pharmacological and Toxicological Methods
#13
REVIEW
Alexander Starr, Kelly L Jordan-Sciutto, Eugene Mironets
The persistence of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) in the era of effective antiretroviral therapy suggests that modern HIV neuropathogenesis is driven, at least in part, by mechanisms distinct from the viral life cycle. Identifying more subtle mechanisms is complicated by frequent comorbidities in HIV+ populations. One of the common confounds is substance abuse, with cannabis being the most frequently used psychoactive substance among people living with HIV. The psychoactive effects of cannabis use can themselves mimic, and perhaps magnify, the cognitive deficits observed in HAND; however, the neuromodulatory and anti-inflammatory properties of cannabinoids may counter HIV-induced excitotoxicity and neuroinflammation...
June 26, 2021: Viruses
#14
JOURNAL ARTICLE
Lindsay M Roth, Cagla Akay-Espinoza, Judith B Grinspan, Kelly L Jordan-Sciutto
Despite combined antiretroviral therapy (cART), HIV-associated neurocognitive disorder (HAND) affects 30-50% of HIV-positive patients. Importantly, persistent white matter pathologies, specifically corpus callosum thinning and disruption of white matter microstructures observed in patients with HAND despite viral control through cART, raise the possibility that HIV infection in the setting of suboptimal cART may perturb oligodendrocyte (OL) maturation, function and/or survival, influencing HAND persistence in the cART era...
May 31, 2021: Glia
#15
JOURNAL ARTICLE
Kelly L Jordan-Sciutto
Persistence of cognitive, behavioral and, to a lesser extent, motor dysfunction in People living with HIV (PLWH) despite viral suppression has raised the question about the potential contribution of antiretroviral (ARV) compounds themselves. Converging clinical and experimental evidence support a contribution of ARV compounds. In this issue we explore the existing clinical evidence on the impact of antiretroviral therapy (ART) on the CNS across the age continuum and in women. We further examine cell type specific effects of ARV drugs as well as the class specific effects...
March 2, 2021: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
#16
JOURNAL ARTICLE
Sean K Ryan, Kelly L Jordan-Sciutto, Stewart A Anderson
This protocol establishes a tri-culture of hiPSC-derived neurons, astrocytes, and microglia for the study of cellular interactions during homeostasis, injury, and disease. This system allows for mechanistic studies that can identify the roles of individual cell types in disease and injury response in a physiologically relevant, all-human system. This protocol utilizes and modifies prior differentiations. Limitations include the prolonged maturation of human astrocytes and neurons and scalability. For complete details on the use and execution of this protocol, please refer to Ryan et al...
December 18, 2020: STAR protocols
#17
JOURNAL ARTICLE
Lindsay M Roth, Bassam Zidane, Lindsay Festa, Raj Putatunda, Micah Romer, Hubert Monnerie, Kelly L Jordan-Sciutto, Judith B Grinspan
Regardless of adherence to combined antiretroviral therapy, white matter and myelin pathologies persist in patients with HIV-associated neurocognitive disorders, a spectrum of cognitive, motor, and behavioral impairments. We hypothesized that antiretroviral therapy alters the maturation of oligodendrocytes which synthesize myelin. We tested whether specific frontline integrase strand transfer inhibitors would alter oligodendrocyte differentiation and myelination. To model the effect of antiretrovirals on oligodendrocytes, we stimulated primary rat oligodendrocyte precursor cells to differentiate into mature oligodendrocytes in vitro in the presence of therapeutically relevant concentrations of elvitegravir or raltegravir and then assessed differentiation with lineage specific markers...
February 2021: Glia
#18
Sean K Ryan, Michael V Gonzalez, James P Garifallou, Frederick C Bennett, Kimberly S Williams, Nathaniel P Sotuyo, Eugene Mironets, Kieona Cook, Hakon Hakonarson, Stewart A Anderson, Kelly L Jordan-Sciutto
No abstract text is available yet for this article.
May 12, 2020: Stem Cell Reports
#19
JOURNAL ARTICLE
Sean K Ryan, Michael V Gonzalez, James P Garifallou, Frederick C Bennett, Kimberly S Williams, Nathaniel P Sotuyo, Eugene Mironets, Kieona Cook, Hakon Hakonarson, Stewart A Anderson, Kelly L Jordan-Sciutto
HIV-associated neurocognitive disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a representative model. We developed a human-induced pluripotent stem cell (hiPSC)-based model, independently differentiating hiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV infection and ART. Single-cell RNA sequencing analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types...
March 6, 2020: Stem Cell Reports
#20
JOURNAL ARTICLE
Sarah Bond, Claudia Lopez-Lloreda, Patrick J Gannon, Cagla Akay-Espinoza, Kelly L Jordan-Sciutto
The proposed molecular mechanisms underlying neurodegenerative pathogenesis are varied, precluding the development of effective therapies for these increasingly prevalent disorders. One of the most consistent observations across neurodegenerative diseases is the phosphorylation of eukaryotic initiation factor 2α (eIF2α). eIF2α is a translation initiation factor, involved in cap-dependent protein translation, which when phosphorylated causes global translation attenuation. eIF2α phosphorylation is mediated by 4 kinases, which, together with their downstream signaling cascades, constitute the integrated stress response (ISR)...
January 8, 2020: Journal of Neuropathology and Experimental Neurology
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