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Hiv associated neurocognitive disorder

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https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#1
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212619/brain-and-liver-pathology-amyloid-deposition-and-interferon-responses-among-older-hiv-positive-patients-in-the-late-haart-era
#2
Isaac H Solomon, Umberto De Girolami, Sukrutha Chettimada, Vikas Misra, Elyse J Singer, Dana Gabuzda
BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons...
February 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28178646/menin-mediates-tat-induced-neuronal-apoptosis-in-brain-frontal-cortex-of-siv-infected-macaques-and-in-tat-treated-cells
#3
Jun Wang, Yu Zhang, Qiping Xu, Jinhua Qiu, Honghua Zheng, Xiang Ye, Yuhua Xue, Yongmei Yin, Zhou Zhang, Ying Liu, Yanling Hao, Qiang Wei, Wei Wang, Kazuyasu Mori, Shuji Izumo, Ryuji Kubota, Yiming Shao, Hui Qin Xing
The molecular mechanisms involved in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain poorly understood. It has been recently reported that HIV-1 Tat transactivation requires menin, suggesting that menin may be involved in HAND pathogenesis. But the role of menin is not clear. Here, we found that protein level of menin was increased in simian-human immunodeficiency chimeric virus (SHIV)-SF162.P4 and simian immunodeficiency virus (SIV) sm543-3-infected rhesus macaques compared with the controls by immunohistochemistry (IHC) and western blot...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166799/toll-like-receptor-3-activation-selectively-reverses-hiv-latency-in-microglial-cells
#4
David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Stephanie Milne, Biswajit Das, Curtis Dobrowolski, Roxana Rojas, Jonathan Karn
BACKGROUND: Multiple toll-like receptors (TLRs) are expressed in cells of the monocytic lineage, including microglia, which constitute the major reservoir for human immunodeficiency virus (HIV) infection in the brain. We hypothesized that TLR receptor mediated responses to inflammatory conditions by microglial cells in the central nervous system (CNS) are able to induce latent HIV proviruses, and contribute to the etiology of HIV-associated neurocognitive disorders. RESULTS: Newly developed human microglial cell lines (hµglia), obtained by immortalizing human primary microglia with simian virus-40 (SV40) large T antigen and the human telomerase reverse transcriptase, were used to generate latently infected cells using a single-round HIV virus carrying a green fluorescence protein reporter (hµglia/HIV, clones HC01 and HC69)...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28160772/renal-safety-of-lithium-in-hiv-infected-patients-established-on-tenofovir-disoproxil-fumarate-containing-antiretroviral-therapy-analysis-from-a-randomized-placebo-controlled-trial
#5
Eric H Decloedt, Maia Lesosky, Gary Maartens, John A Joska
BACKGROUND: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. OBJECTIVE: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment...
February 4, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28155864/aberrant-neuronal-dynamics-during-working-memory-operations-in-the-aging-hiv-infected-brain
#6
Tony W Wilson, Amy L Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R Robertson, Howard S Fox, Susan Swindells
Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG)...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28149649/hepatitis-c-virus-infection-and-neurological-and-psychiatric-disorders-a-review
#7
REVIEW
Lydia Yarlott, Eleanor Heald, Daniel Forton
An association between hepatitis C virus infection and neuropsychiatric symptoms has been proposed for some years. A variety of studies have been undertaken to assess the nature and severity of these symptoms, which range from fatigue and depression to defects in attention and verbal reasoning. There is evidence of mild neurocognitive impairment in some patients with HCV infection, which is not fully attributable to liver dysfunction or psychosocial factors. Further evidence of a biological cerebral effect has arisen from studies using magnetic resonance spectroscopy; metabolic abnormalities correlate with cognitive dysfunction and resemble the patterns of neuroinflammation that have been described in HIV infection...
March 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28133717/dopamine-increases-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-implications-for-substance-abuse-and-hiv-neuropathogenesis
#8
Tina M Calderon, Dionna W Williams, Lillie Lopez, Eliseo A Eugenin, Laura Cheney, Peter J Gaskill, Mike Veenstra, Kathryn Anastos, Susan Morgello, Joan W Berman
In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14(+)CD16(+) monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14(+)CD16(+) monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND...
January 29, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28127989/psychiatric-symptom-burden-in-older-people-living-with-hiv-with-and-without-cognitive-impairment-the-ucsf-hiv-over-60-cohort-study
#9
Benedetta Milanini, Stephanie Catella, Brandon Perkovich, Pardis Esmaeili-Firidouni, Lauren Wendelken, Robert Paul, Meredith Greene, Robin Ketelle, Victor Valcour
Psychiatric comorbidities are common in people living with HIV (PLWH) and adversely affect life satisfaction, treatment adherence and disease progression. There are few data to inform the burden of psychiatric symptoms in older PLWH, a rapidly growing demographic in the U.S. We performed a cross-sectional analysis to understand the degree to which symptom burden was associated with cognitive disorders in PLWH over age 60. Participants completed a standardized neuropsychological battery and were assigned cognitive diagnoses using Frascati criteria...
January 27, 2017: AIDS Care
https://www.readbyqxmd.com/read/28127697/differential-mechanisms-of-inflammation-and-endothelial-dysfunction-by-hiv-1-subtype-b-and-recombinant-crf02_ag-tat-proteins-on-human-brain-microvascular-endothelial-cells-implications-for-viral-neuropathogenesis
#10
Biju Bhargavan, Georgette D Kanmogne
The recombinant HIV-1 CRF02_AG is prevalent in West-Central Africa but its effects on the blood-brain barrier (BBB) and HIV-associated neurocognitive disorders (HAND) are not known. We analyzed the effects of Tat from HIV-1 subtype-B (Tat.B) and CRF02_AG (Tat.AG) on primary human brain microvascular endothelial cells (HBMEC), the major BBB component. Exposure of HBMEC to Tat.B increased IL-6 expression and transcription by 9- (P < 0.001) and 113-fold (P < 0.001), respectively, whereas Tat.AG increased IL-6 expression and transcription by 2...
January 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28122624/hiv-induces-expression-of-complement-component-c3-in-astrocytes-by-nf-%C3%AE%C2%BAb-dependent-activation-of-interleukin-6-synthesis
#11
Jadwiga Nitkiewicz, Alejandra Borjabad, Susan Morgello, Jacinta Murray, Wei Chao, Luni Emdad, Paul B Fisher, Mary Jane Potash, David J Volsky
BACKGROUND: Abnormal activation of the complement system contributes to some central nervous system diseases but the role of complement in HIV-associated neurocognitive disorder (HAND) is unclear. METHODS: We used real-time PCR and immunohistochemistry to detect complement expression in postmortem brain tissue from HAND patients and controls. To further investigate the basis for viral induction of gene expression in the brain, we studied the effect of HIV on C3 expression by astrocytes, innate immune effector cells, and targets of HIV...
January 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28122474/screening-for-neurocognitive-impairment-in-hiv-positive-adults-aged-50-years-and-older-montreal-cognitive-assessment-relates-to-self-reported-and-clinician-rated-everyday-functioning
#12
P L Fazeli, K B Casaletto, E Paolillo, R C Moore, D J Moore, The Hnrp Group
As the HIV+ population ages, the risk for and need to screen for HIV-associated neurocognitive disorders (HAND) increases. The aim of this study is to determine the utility and ecological validity of the Montreal Cognitive Assessment (MoCA) among older HIV+ adults. A total of 100 HIV+ older adults aged 50 years or over completed a comprehensive neuromedical and neurocognitive battery, including the MoCA and several everyday functioning measures. The receiver operating characteristic curve indicates ≤26 as the optimal cut-off balancing sensitivity (84...
January 26, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28110422/interventions-for-neurocognitive-dysfunction
#13
REVIEW
Jacqueline Ellero, Michal Lubomski, Bruce Brew
PURPOSE OF REVIEW: This study aimed to evaluate current barriers to HIV cure strategies and interventions for neurocognitive dysfunction with a particular focus on recent advancements over the last 3 years. RECENT FINDINGS: Optimal anti-retroviral therapy (ART) poses challenges to minimise neurotoxicity, whilst ensuring blood-brain barrier penetration and minimising the risk of cerebrovascular disease. CSF biomarkers, BCL11B and neurofilament light chain may be implicated with a neuroinflammatory cascade leading to cognitive impairment...
January 21, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28108972/a-comparison-of-the-sensitivity-stability-and-reliability-of-three-diagnostic-schemes-for-hiv-associated-neurocognitive-disorders
#14
Savanna M Tierney, David P Sheppard, Victoria M Kordovski, Marika P Faytell, Gunes Avci, Steven Paul Woods
HIV-associated neurocognitive disorders (HAND) occur in approximately 50% of HIV-infected individuals, yet available diagnostic criteria yield varying prevalence rates. This study examined the frequency, reliability, and sensitivity to everyday functioning problems of three HAND diagnostic criteria (DSM-5, Frascati, Gisslén). Participants included 361 adults with HIV disease and 199 seronegative adults. Neurocognitive status as defined by each of the three diagnostic systems was determined via a comprehensive neuropsychological battery...
January 20, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28108876/concordance-between-self-report-and-performance-based-measures-of-everyday-functioning-in-hiv-associated-neurocognitive-disorders
#15
Talia N Shirazi, Angela C Summers, Bryan R Smith, Sally R Steinbach, Suad Kapetanovic, Avindra Nath, Joseph Snow
Self-report is typically used to differentiate between asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) in the assessment of HIV-associated neurocognitive disorders (HAND). Yet, it is unclear whether the lack of self-reported functional impairments in individuals with ANI is indicative of a genuine absence of functional impairment, or of inaccurate self-reports. In the present study, we examined the relationship between previously validated self-report (patient's assessment of own functioning inventory; instrumental activities of daily living inventory) and performance-based (the Texas Functional Living Scale) measures of functional abilities in 112 virologically-controlled HIV-infected, and 40 well-matched, HIV-uninfected participants...
January 20, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#16
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28101920/quantitative-proteomic-analysis-of-hiv-1-tat-induced-dysregulation-in-sh-sy5y-neuroblastoma-cells
#17
Tariq Ganief, Putuma Gqamana, Shaun Garnett, Jackie Hoare, Dan J Stein, John Joska, Nelson Soares, Jonathan M Blackburn
Despite affecting up to 70% of HIV-positivepatients and being the leading cause of dementia in patients under 40 years, the molecular mechanisms involved in the onset of HIV-associated neurocognitive disorders (HAND) are not well understood. To address this, we performed SILAC-based quantitative proteomic analysis on HIV-Tat treated SH-SY5Y neuroblastoma cells. Isolated protein was fractionated by SDS-PAGE and analysed by nLC-MS/MS on an Orbitrap Velos. Using MaxQuant, we identified and quantified 3077 unique protein groups, of which 407 were differentially regulated...
January 19, 2017: Proteomics
https://www.readbyqxmd.com/read/28099190/coagulation-imbalance-and-neurocognitive-functioning-in-older-hiv-adults-on-suppressive-antiretroviral-therapy
#18
Jessica L Montoya, Jennifer Iudicello, Hannah A Oppenheim, Pariya L Fazeli, Michael Potter, Qing Ma, Paul J Mills, Ronald J Ellis, Igor Grant, Scott L Letendre, David J Moore
OBJECTIVES: To compare plasma biomarkers of coagulation between HIV-infected individuals and HIV-uninfected controls and to assess the impact of disturbances in coagulation on neurocognitive functioning in HIV. DESIGN: Cross-sectional study of 66 antiretroviral therapy-treated virally suppressed HIV-infected and 34 HIV-uninfected older (≥50 years of age) adults. METHODS: Participants completed standardized neurobehavioral and neuromedical assessments...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28074940/alpha7-nicotinic-acetylcholine-receptor-is-required-for-amyloid-pathology-in-brain-endothelial-cells-induced-by-glycoprotein-120-methamphetamine-and-nicotine
#19
Liqun Liu, Jingyi Yu, Li Li, Bao Zhang, Lingjuan Liu, Chun-Hua Wu, Ambrose Jong, Ding-An Mao, Sheng-He Huang
One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070871/treating-hiv-infection-in-the-central-nervous-system
#20
REVIEW
A Calcagno, G Di Perri, S Bonora
Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management...
February 2017: Drugs
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