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.
Highlights
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)
Despite the success of combination antiretroviral therapy in diminishing the prevalence of progressive HIV-1 encephalopathy (PHE), high rates of chronic neurological impairment are still being reported in HIV-1 seropositive children[1,2,3,4]
HIV-1 Tg rats exhibited a profound alteration in the progression of temporal processing assessed using prepulse inhibition
Summary
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). 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. The HIV-1 transgenic (Tg) rat may be used to model the effects of long-term HIV-1 viral protein exposure on the development and progression of chronic neurological deficits observed in children perinatally infected with HIV-16. A longitudinal analysis of temporal processing deficits, a potential underlying dimension of neurocognitive impairment in HIV-1, may provide insight into the effect of long-term HIV-1 viral protein exposure on the development of chronic neurologic impairment in HIV-1 seropositive children. HIV-1 Tg animals, in comparison to control www.nature.com/scientificreports/
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