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      Progression of temporal processing deficits in the HIV-1 transgenic rat

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      Scientific Reports
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          Abstract

          The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes, was used to investigate the effect(s) of long-term HIV-1 viral protein exposure on chronic neurocognitive deficits observed in pediatric HIV-1 (PHIV). A longitudinal experimental design was used to assess the progression of temporal processing deficits, a potential underlying dimension of neurocognitive impairment in HIV-1. Gap prepulse inhibition (gap-PPI), a translational experimental paradigm, was conducted every thirty days from postnatal day (PD) 30 to PD 180. HIV-1 Tg animals, regardless of sex, displayed profound alterations in the development of temporal processing, assessed using prepulse inhibition. A differential sensitivity to the manipulation of interstimulus interval was observed in HIV-1 Tg animals in comparison to control animals. Moreover, presence of the HIV-1 transgene was diagnosed with 90.8% accuracy using measures of prepulse inhibition and temporal sensitivity. Progression of temporal processing deficits in the HIV-1 Tg rat affords a relatively untapped opportunity to increase our mechanistic understanding of the role of long-term exposure to HIV-1 viral proteins, observed in pediatric HIV-1, in the development of chronic neurological impairment, as well as suggesting an innovative clinical diagnostic screening tool.

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          Most cited references54

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          Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.

          Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. Similar deficits in PPI are produced in rats by pharmacological or developmental manipulations. These experimentally induced PPI deficits in rats are clearly not animal models of schizophrenia per se, but appear to provide models of sensorimotor gating deficits in schizophrenia patients that have face, predictive, and construct validity. In rodents, disruptions in PPI of startle are produced by: stimulation of D2 dopamine (DA) receptors, produced by amphetamine or apomorphine; activation of serotonergic systems, produced by serotonin (5-HT) releasers or direct agonists at multiple serotonin receptors; and blockade of N-methyl-D-aspartate (NMDA) receptors, produced by drugs such as phencyclidine (PCP). Accordingly, dopaminergic, serotonergic, and glutamatergic models of disrupted PPI have evolved and have been applied to the identification of potential antipsychotic treatments. In addition, some developmental manipulations, such as isolation rearing, have provided non-pharmacological animal models of the PPI deficits seen in schizophrenia. This review summarizes and evaluates studies assessing the effects of systemic drug administrations on PPI in rats. Studies examining systemic drug effects on PPI in rats prior to January 15, 2001 were compiled and organized into six annotated appendices. Based on this catalog of studies, the specific advantages and disadvantages of each of the four main PPI models used in the study of antipsychotic drugs were critically evaluated. Despite some notable inconsistencies, the literature provides strong support for significant disruptions in PPI in rats produced by DA agonists, 5-HT2 agonists, NMDA antagonists, and isolation rearing. Each of these models exhibits sensitivity to at least some antipsychotic medications. While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotics, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics. The 5-HT PPI model is less generally sensitive to antipsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychotics that act upon multiple receptors. The deficits in PPI produced by NMDA antagonists appear to be more sensitive to clozapine-like atypical antipsychotics than to typical antipsychotics. Hence, despite some exceptions to this generalization, the NMDA PPI model might aid in the identification of novel or atypical antipsychotic medications. Studies of drug effects on PPI in rats have generated four distinctive models that have utility in the identification of antipsychotic medications. Because each of these models has specific advantages and disadvantages, the choice of model to be used depends upon the question being addressed. This review should help to guide such decisions.
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            HIV and antiretroviral therapy in the brain: neuronal injury and repair.

            Approximately 40 million people worldwide are infected with human immunodeficiency virus (HIV). Despite HIV's known propensity to infect the CNS and cause neurological disease, HIV neurocognitive disorders remain under-recognized. Although combination antiretroviral therapy has improved the health of millions of those living with HIV, the penetration into the CNS of many such therapies is limited, and patients' quality of life continues to be diminished by milder, residual neurocognitive impairment. Synaptodendritic neuronal injury is emerging as an important mediator of such deficits in HIV. By carefully selecting specific antiretrovirals and supplementing them with neuroprotective agents, physicians might be able to facilitate innate CNS repair, promoting enhanced synaptodendritic plasticity, neural function and clinical neurological status.
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              Prestimulus effects on human startle reflex in normals and schizophrenics.

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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                06 September 2016
                2016
                : 6
                : 32831
                Affiliations
                [1 ]Program in Behavioral Neuroscience Department of Psychology University of South Carolina Columbia , SC 29208, USA.
                Author notes
                Article
                srep32831
                10.1038/srep32831
                5011765
                27596023
                76315bb1-8c2b-45af-987d-4589f1ab194e
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 05 March 2016
                : 15 August 2016
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