Nonmedical use of prescription opioids peaks during late adolescence, a developmental period associated with the maturation of higher-order cognitive processes. To date, however, how chronic adolescent oxycodone (OXY) self-administration alters neurobehavioral (i.e.
View Article and Find Full Text PDFMixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo.
View Article and Find Full Text PDFMixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 mRNA from cortical mixed glia was evaluated and .
View Article and Find Full Text PDFAdverse neurological and psychiatric outcomes, collectively termed the post-acute sequelae of SARS-CoV-2 infection (PASC), persist in adults clinically recovered from COVID-19. Effective therapeutic interventions are fundamental to reducing the burden of PASC, necessitating an investigation of the pathophysiology underlying the debilitating neurological symptoms associated with the condition. Herein, eight non-human primates (Wild-Caught African Green Monkeys, =4; Indian Rhesus Macaques, =4) were inoculated with the SARS-CoV-2 isolate USA-WA1/2020 by either small particle aerosol or via multiple routes.
View Article and Find Full Text PDFApproximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations.
View Article and Find Full Text PDFMicroglia, which are productively infected by HIV-1, are critical for brain development and maturation, as well as synaptic plasticity. The pathophysiology of HIV-infected microglia and their role in the pathogenesis of HIV-1-associated neurocognitive and affective alterations, however, remains understudied. Three complementary aims were undertaken to critically address this knowledge gap.
View Article and Find Full Text PDFMicroglia, which are productively infected by HIV-1, are critical for brain development and maturation, as well as synaptic plasticity. The pathophysiology of HIV-infected microglia and their role in the pathogenesis of HIV-1-associated neurocognitive and affective alterations, however, remains understudied. Three complementary aims were undertaken to critically address this knowledge gap.
View Article and Find Full Text PDFIndependently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit as evidenced by both clinical and preclinical studies; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing experience with both sucrose and cocaine self-administration, a pretest-posttest experimental design was utilized to evaluate preference judgment, a simple form of decision-making dependent upon the integrity of frontal-striatal circuit function. During the pretest assessment, male rats exhibited a clear preference for cocaine, whereas female animals preferred sucrose.
View Article and Find Full Text PDFIndividuals living with human immunodeficiency virus type 1 (HIV-1) exhibit an increased prevalence of neuropsychiatric comorbities (e.g., apathy) relative to their seronegative counterparts.
View Article and Find Full Text PDFThe prevalence of HIV-1 associated neurocognitive disorders (HAND) is significantly greater in older, relative to younger, HIV-1 seropositive individuals; the neural pathogenesis of HAND in older HIV-1 seropositive individuals, however, remains elusive. To address this knowledge gap, abnormal protein aggregates (i.e.
View Article and Find Full Text PDFDue to the widespread access to, and implementation of, combination antiretroviral therapy, individuals perinatally infected with human immunodeficiency virus type 1 (HIV-1) are living into adolescence and adulthood. Perinatally infected adolescents living with HIV-1 (pALHIV) are plagued by progressive, chronic neurocognitive impairments; the pathophysiological mechanisms underlying these deficits, however, remain understudied. A longitudinal experimental design from postnatal day (PD) 30 to PD 180 was utilized to establish the development of pyramidal neurons, and associated dendritic spines, from layers II-III of the medial prefrontal cortex (mPFC) in HIV-1 transgenic (Tg) and control animals.
View Article and Find Full Text PDFIndividuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.
View Article and Find Full Text PDFThe persistence of HIV-1 viral reservoirs in the brain, despite treatment with combination antiretroviral therapy (cART), remains a critical roadblock for the development of a novel cure strategy for HIV-1. To enhance our understanding of viral reservoirs, two complementary studies were conducted to (1) evaluate the HIV-1 mRNA distribution pattern and major cell type expressing HIV-1 mRNA in the HIV-1 transgenic (Tg) rat, and (2) validate our findings by developing and critically testing a novel biological system to model active HIV-1 infection in the rat. First, a restricted, region-specific HIV-1 mRNA distribution pattern was observed in the HIV-1 Tg rat.
View Article and Find Full Text PDFHIV-1 infection affects approximately 37 million individuals, and approximately 50% of seropositive individuals will develop symptoms of clinical depression and/or apathy. Dysfunctions of both serotonergic and dopaminergic neurotransmission have been implicated in the pathogenesis of motivational alterations. The present study evaluated the efficacy of a SSRI (escitalopram) in the HIV-1 transgenic (Tg) rat.
View Article and Find Full Text PDFIt has been well studied that the EcoHIV infected mouse model is of significant utility in investigating HIV associated neurological complications. Establishment of the EcoHIV infected rat model for studies of drug abuse and neurocognitive disorders, would be beneficial in the study of neuroHIV and HIV-1 associated neurocognitive disorders (HAND). In the present study, we demonstrate the successful creation of a rat model of active HIV infection using chimeric HIV (EcoHIV).
View Article and Find Full Text PDFHydrophobic tissue clearing methods are easily adjustable, fast, and low-cost procedures that allows for the study of a molecule of interest in unaltered tissue samples. Traditional immunolabeling procedures require cutting the sample into thin sections, which restricts the ability to label and examine intact structures. However, if brain tissue can remain intact during processing, structures and circuits can remain intact for the analysis.
View Article and Find Full Text PDFChronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.
View Article and Find Full Text PDFJ Neuroimmune Pharmacol
December 2020
Corrected sentence in Interactions between the Effects of Drug Use and HIV-1 Infection Leads to Accelerated Disease Progression: "White matter damage (Tang et al. 2015; Alakkas et al. 2019), mitochondrial dysfunction (Buch et al.
View Article and Find Full Text PDFThe fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1 infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit. However, chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased dopamine.
View Article and Find Full Text PDFIt has been reported that the size and shape of dendritic spines is related to their structural plasticity. To identify the morphological structure of pyramidal neurons and dendritic spines, a ballistic labeling technique can be utilized. In the present protocol, pyramidal neurons are labeled with DilC18(3) dye and analyzed using neuronal reconstruction software to assess neuronal morphology and dendritic spines.
View Article and Find Full Text PDFThe persistence of HIV-1 associated neurocognitive disorders (HAND) in the post-cART era, afflicting between 40 and 70% of HIV-1 seropositive individuals, supports a critical need for the development of adjunctive therapeutic treatments. Selective estrogen receptor β agonists, including S-Equol (SE), have been implicated as potential therapeutic targets for the treatment of neurocognitive disorders. In the present study, the therapeutic efficacy of 0.
View Article and Find Full Text PDFHIV-1-associated neurocognitive disorders (HAND), characterized by alterations in the core components of cognitive function and age-related disease progression, persist in the post-cART era. However, the neurobehavioral mechanisms that mediate alterations in the core components of cognitive function and the progression of neurocognitive impairments have yet to be systematically evaluated. To address this knowledge gap, statistical mediation analysis was assessed, providing a critical opportunity to empirically evaluate putative neurobehavioral mechanisms underlying HAND.
View Article and Find Full Text PDFDue to the sustained prevalence of human immunodeficiency virus (HIV)-1 associated neurocognitive disorders (HAND) in the post-combination antiretroviral therapy (cART) era, as well as the increased prevalence of older HIV-1 seropositive individuals, there is a critical need to develop adjunctive therapeutics targeted at preserving and/or restoring neurocognitive function. To address this knowledge gap, the present study examined the utility of S-Equol (SE), a phytoestrogen produced by gut microbiota, as an innovative therapeutic strategy. A signal detection operant task with varying signal durations (1,000, 500, 100 ms) was utilized to assess sustained attention in HIV-1 transgenic (Tg) and control animals.
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