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Kelly Jordan Sciutto

Hubert Monnerie, Micah Romer, Brigid K Jensen, John S Millar, Kelly L Jordan-Sciutto, Sangwon F Kim, Judith B Grinspan
The formation of the myelin membrane of the oligodendrocyte in the CNS is a fundamental process requiring the coordinated synthesis of many different components. The myelin membrane is particularly rich in lipids, however, the regulation of these synthesis of these is not understood. In other cell types, including Schwann cells, the myelin-forming cells of the PNS, lipid synthesis is tightly regulated by the sterol regulatory element-binding protein (SREBP) family of transcription factors, but this has not been previously shown in oligodendrocytes...
July 6, 2016: Journal of Neurochemistry
Daniel J Colacurcio, Jacob W Zyskind, Kelly L Jordan-Sciutto, Cagla Akay Espinoza
MDMx/MDM4 is a negative regulator of the p53 tumor suppressor protein and is necessary for survival in dividing cells. MDMx is also expressed in postmitotic neurons, with prosurvival roles that are independent of its extensively described roles in carcinogenesis. We and others have shown a role for MDMx loss in neuronal death in vitro and in vivo in several neurodegenerative diseases. Further, we have recently shown that MDMx is targeted for proteolytic degradation by calcium-dependent proteases, calpains, in neurons in vitro, and that MDMx overexpression provided partial neuroprotection in a model of HIV-associated neurodegeneration...
November 16, 2015: Neuroscience Letters
Brigid K Jensen, Hubert Monnerie, Maggie V Mannell, Patrick J Gannon, Cagla Akay Espinoza, Michelle A Erickson, Annadora J Bruce-Keller, Benjamin B Gelman, Lisa A Briand, R Christopher Pierce, Kelly L Jordan-Sciutto, Judith B Grinspan
Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance...
November 2015: Journal of Neuropathology and Experimental Neurology
Jacob W Zyskind, Ying Wang, Giyong Cho, Jenhao H Ting, Dennis L Kolson, David R Lynch, Kelly L Jordan-Sciutto
The transcription factor E2F1 activates gene targets required for G1 -S phase progression and for apoptosis, and exhibits increased expression levels in neurons in several CNS diseases including HIV encephalitis, Alzheimer disease, and Parkinson's Disease. While E2F1 is known to regulate cell viability through activation of caspases, here we present evidence supporting the involvement of E2F1 in N-methyl-d-aspartate (NMDA) receptor-dependent, HIV-induced neuronal death mediated by calpains. Using an in vitro model of HIV-induced neurotoxicity that is dependent on NMDA receptor and calpain activation, we have shown that cortical neurons lacking functional E2F1 are less susceptible to neuronal death...
March 2015: Journal of Neurochemistry
Alexander J Gill, Colleen E Kovacsics, Stephanie A Cross, Patricia J Vance, Lorraine L Kolson, Kelly L Jordan-Sciutto, Benjamin B Gelman, Dennis L Kolson
Heme oxygenase-1 (HO-1) is an inducible, detoxifying enzyme that is critical for limiting oxidative stress, inflammation, and cellular injury within the CNS and other tissues. Here, we demonstrate a deficiency of HO-1 expression in the brains of HIV-infected individuals. This HO-1 deficiency correlated with cognitive dysfunction, HIV replication in the CNS, and neuroimmune activation. In vitro analysis of HO-1 expression in HIV-infected macrophages, a primary CNS HIV reservoir along with microglia, demonstrated a decrease in HO-1 as HIV replication increased...
October 2014: Journal of Clinical Investigation
Lena Al-Harthi, Shilpa Buch, Jonathan D Geiger, Howard E Gendelman, Johnny J He, Kelly L Jordan-Sciutto, Dennis L Kolson, Jay Rappaport, Sabita Roy, Jialin Zheng, Howard S Fox
On May 23, 2013 scientific leaders in the neuroAIDS community met at the University of Nebraska Medical Center to discuss cellular interaction and signaling for the third annual human immunodeficiency virus and neuroAIDS colloquium. The meeting continues a series of contemporary scientific issues related to how virus effects the nervous system. In 2011 the focus was on animal models and in 2012 in biomarkers. Here, our 2013 meeting featured ten presentations from outstanding scientists examining how inter- and intra-cellular processes contribute to neuropathogenesis...
June 2014: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Jenhao H Ting, David R Marks, Stephanie S Schleidt, Joanna N Wu, Jacob W Zyskind, Kathryn A Lindl, Julie A Blendy, R Christopher Pierce, Kelly L Jordan-Sciutto
Aberrant expression and activation of the cell cycle protein E2F1 in neurons has been implicated in many neurodegenerative diseases. As a transcription factor regulating G1 to S phase progression in proliferative cells, E2F1 is often up-regulated and activated in models of neuronal death. However, despite its well-studied functions in neuronal death, little is known regarding the role of E2F1 in the mature brain. In this study, we used a combined approach to study the effect of E2F1 gene disruption on mouse behavior and brain biochemistry...
June 2014: Journal of Neurochemistry
Cagla Akay, Michael Cooper, Akinleye Odeleye, Brigid K Jensen, Michael G White, Fair Vassoler, Patrick J Gannon, Joseph Mankowski, Jamie L Dorsey, Alison M Buch, Stephanie A Cross, Denise R Cook, Michelle-Marie Peña, Emily S Andersen, Melpo Christofidou-Solomidou, Kathryn A Lindl, M Christine Zink, Janice Clements, R Christopher Pierce, Dennis L Kolson, Kelly L Jordan-Sciutto
HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % of HIV(+) patients despite the success of combination antiretroviral drug therapy (cART) in the periphery. Of note, potential toxicity of antiretroviral drugs in the central nervous system (CNS) remains remarkably underexplored and may contribute to the persistence of HAND in the cART era. Previous studies have shown antiretrovirals (ARVs) to be neurotoxic in the peripheral nervous system in vivo and in peripheral neurons in vitro...
February 2014: Journal of Neurovirology
Daniel J Colacurcio, Alyssa Yeager, Dennis L Kolson, Kelly L Jordan-Sciutto, Cagla Akay
Neuronal damage in HIV-associated Neurocognitive Disorders (HAND) has been linked to inflammation induced by soluble factors released by HIV-infected, and non-infected, activated macrophages/microglia (HIV M/M) in the brain. It has been suggested that aberrant neuronal cell cycle activation determines cell fate in response to these toxic factors. We have previously shown increased expression of cell cycle proteins such as E2F1 and phosphorylated pRb in HAND midfrontal cortex in vivo and in primary neurons exposed to HIV M/M supernatants in vitro...
November 2013: Molecular and Cellular Neurosciences
Ying Wang, Jacob W Zyskind, Daniel J Colacurcio, Kathryn A Lindl, Jenhao H Ting, Galina Grigoriev, Kelly L Jordan-Sciutto
Necrosis and apoptosis are well established as two primary cell death pathways. Mixed neuroglial cultures are commonly used to study cell death mechanisms in neural cells. However, the ages of these cultures vary across studies and little attention has been paid to how cell death processes may change as the cultures mature. To clarify whether neuroglial culture age affects cell death mechanisms, we treated 1- and 3-week-old neuroglial cultures with either the excitotoxic stimulus, N-methyl-D-aspartate (NMDA), or with the oxidative stressor, hydrogen peroxide (H2O2)...
December 19, 2012: Neuroreport
Stephanie A Cross, Denise R Cook, Anthony W S Chi, Patricia J Vance, Lorraine L Kolson, Bethany J Wong, Kelly L Jordan-Sciutto, Dennis L Kolson
Despite antiretroviral therapy (ART), HIV infection promotes cognitive dysfunction and neurodegeneration through persistent inflammation and neurotoxin release from infected and/or activated macrophages/microglia. Furthermore, inflammation and immune activation within both the CNS and periphery correlate with disease progression and morbidity in ART-treated individuals. Accordingly, drugs targeting these pathological processes in the CNS and systemic compartments are needed for effective, adjunctive therapy...
November 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Denise R Cook, Amy J Gleichman, Stephanie A Cross, Shachee Doshi, Wenzhe Ho, Kelly L Jordan-Sciutto, David R Lynch, Dennis L Kolson
Excitotoxic neuronal damage via over-activation of the NMDA receptor has been implicated in many neurodegenerative diseases. In vitro modeling of excitotoxic injury has shown that activation of G-protein coupled receptors (GPCRs) counteracts such injury through modulation of neuronal pro-survival pathways and/or NMDA receptor signaling. We have previously demonstrated that the GPCR APJ and its endogenous neuropeptide ligand apelin can protect neurons against excitotoxicity, but the mechanism(s) of this neuroprotection remain incompletely understood...
September 2011: Journal of Neurochemistry
Sriram Venneti, Paul Le, Daniel Martinez, Katherine W Eaton, Nikhil Shyam, Kelly L Jordan-Sciutto, Bruce Pawel, Jaclyn A Biegel, Alexander R Judkins
Malignant rhabdoid tumors (MRTs) are aggressive tumors associated with mutations in the SMARCB1 gene. In experimental systems, the loss of SMARCB1 is hypothesized to alter p16(INK4A) pathways resulting in the repression of tumor suppressors. To determine whether these pathways are deregulated in human MRT, we used immunohistochemistry on tissue microarrays to evaluate p16(INK4A)/E2F1/RB and p14(ARF)/MDM2/p53 pathways in 25 atypical teratoid/rhabdoid tumors (AT/RT) and 11 non-CNS MRT. p16(INK4A) was negative or showed focal weak expression...
July 2011: Journal of Neuropathology and Experimental Neurology
Michael G White, Ying Wang, Cagla Akay, Kathryn A Lindl, Dennis L Kolson, Kelly L Jordan-Sciutto
Neurocognitive deficits seen in HIV-associated neurocognitive disorders (HANDs) are attributed to the release of soluble factors from CNS-resident, HIV-infected and/or activated macrophages and microglia. To study HIV-associated neurotoxicity, we used our in vitro model in which primary rat neuronal/glial cultures are treated with supernatants from cultured human monocyte-derived macrophages, infected with a CNS-isolated HIV-1 strain (HIV-MDM). We found that neuronal damage, detected as a loss of microtubule-associated protein-2 (MAP2), begins as early as 2h and is preceded by a loss of mitochondrial membrane potential (Δψ(m))...
June 2011: Neuroscience Research
Ying Wang, Nikhil Shyam, Jenhao H Ting, Cagla Akay, Kathryn A Lindl, Kelly L Jordan-Sciutto
As human immunodeficiency virus (HIV) does not induce neuronal damage by direct infection, the mechanisms of neuronal damage or loss in HIV-associated dementia (HAD) remain unclear. We have shown previously that immunoreactivity of transcription factor, E2F1, increases in neurons, localizing predominantly to the cytoplasm, in HIV-associated pathologies. Here we confirm that E2F1 localization is predominantly cytoplasmic in primary postmitotic neurons in vitro and cortical neurons in vivo. To determine whether E2F1 contributes to neuronal death in HAD via transactivation of target promoters, we assessed the mRNA and protein levels of several classical E2F1 transcriptional targets implicated in cell cycle progression and apoptosis in an in vitro model of HIV-induced neurotoxicity and in cortical autopsy tissue from patients infected with HIV...
July 26, 2010: Neuroscience Letters
Kathryn A Lindl, David R Marks, Dennis L Kolson, Kelly L Jordan-Sciutto
Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration...
September 2010: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Alison J B Markowitz, Michael G White, Dennis L Kolson, Kelly L Jordan-Sciutto
Astrocytes perform vital maintenance, functional enhancement, and protective roles for their associated neurons; however these same mechanisms may become deleterious for neurons under some conditions. In this review, we highlight two normally protective pathways, the endoplasmic reticulum (ER) stress response and an endogenous antioxidant response, which may become neurotoxic when activated in astrocytes during the inflammation associated with neurodegeneration. Stimulation of these multifaceted pathways affects a panoply of cellular processes...
July 27, 2007: Cellscience
Kathryn A Lindl, Kelly L Jordan-Sciutto
As organisms designed to depend upon oxygen to sustain life, humans are necessarily and continually exposed to damaging oxidizing agents. As a vital protective measure, oxygen-dependent organisms have developed a highly evolutionarily conserved mechanism for preventing oxidative stress. NF-E2 (nuclear factor (erythroid-derived 2))-related factor-2 (Nrf2) is the primary regulator of this endogenous antioxidant response. Many diseases that plague human society, ranging from various cancers to neurodegenerative diseases, have oxidative stress as a component of their etiology, and thus, much disease research has focused on Nrf2, both as a potential point of biological failure and as a promising therapeutic target...
2008: Methods in Molecular Biology
Ling Dong, Akinleye O Odeleye, Kelly L Jordan-Sciutto, Beth A Winkelstein
The cervical facet joint is implicated as one of the most common sources of chronic neck pain, owing to its rich nociceptive innervation and susceptibility to injurious mechanical loading. Injuries to the facet joint and its ligament can induce inflammation in the joint and spinal cord. Inflammatory molecules which are known to have a role in pain can also stimulate the integrated stress response (ISR). Therefore, we hypothesize that ISR is activated by facet joint injury in a rodent model of pain. To address this hypothesis, we assessed the expression of binding protein (BiP) (also known as growth-related protein 78 (GRP78)), a marker of endoplasmic reticulum stress response, in the dorsal root ganglion (DRG) after painful facet joint injury...
October 3, 2008: Neuroscience Letters
Charleen T Chu, Edward D Plowey, Ying Wang, Vivek Patel, Kelly L Jordan-Sciutto
Neurons may be particularly sensitive to disruptions in transcription factor trafficking. Survival and injury signals must traverse dendrites or axons, in addition to soma, to affect nuclear transcriptional responses. Transcription factors exhibit continued nucleocytoplasmic shuttling; the predominant localization is regulated by binding to anchoring proteins that mask nuclear localization/export signals and/or target the factor for degradation. Two functional groups of karyopherins, importins and exportins, mediate RanGTPase-dependent transport through the nuclear pore...
October 2007: Journal of Neuropathology and Experimental Neurology
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