Abstract
HIV-associated neurocognitive disorders (HAND) remain highly prevalent despite combined antiretroviral therapy (cART). Although the most common forms of HAND are mild and identified through neuropsychological testing, there is evidence that with aging these mild forms become more prevalent and may advance to the most severe form of HAND, HIV-associated dementia. Therefore, novel therapies must be developed that can be used adjunctively with cART to prevent deterioration or restore normal cognitive function. In order to develop innovative treatments, animal models are used for preclinical testing. Ideally, a HAND animal model should portray similar mild cognitive deficits that are found in humans. A mouse model of HAND is discussed, which demonstrates mild behavioral deficits and has been used to investigate cART and novel treatments for HAND. This model also shows correlations between abnormal mouse behavior due to HIV in the brain and pathological parameters such as gliosis and neuronal abnormalities. A recent advancement utilizes the object recognition test to monitor mouse behavior before and after treatment. It is postulated that this model is well suited for preclinical testing of novel therapies and provides correlations of mild cognitive impairment with pathological markers that can give further insight into the pathophysiology of HAND.
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References
Antinori A et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799
Avgeropoulos N et al (1998) SCID mice with HIV encephalitis develop behavioral abnormalities. J Acquir Immune Defic Syndr Hum Retrovirol 18(1):13–20
Bimonte-Nelson H (2015) The maze book: theories, practice, and protocols for testing rodent cognition. Neuromethods Series. Vol. 94. Springer, Humana Press, New York
Clements JE et al (2005) The central nervous system is a viral reservoir in simian immunodeficiency virus--infected macaques on combined antiretroviral therapy: a model for human immunodeficiency virus patients on highly active antiretroviral therapy. J Neuro-Oncol 11(2):180–189
Constantinescu CS et al (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 164(4):1079–1106
Cook JE et al (2005) Highly active antiretroviral therapy and human immunodeficiency virus encephalitis. Ann Neurol 57(6):795–803
Cook-Easterwood J et al (2007) Highly active antiretroviral therapy of cognitive dysfunction and neuronal abnormalities in SCID mice with HIV encephalitis. Exp Neurol 205(2):506–512
Davidson MK, Lindsey JR, Davis JK (1987) Requirements and selection of an animal model. Isr J Med Sci 23(6):551–555
Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31(1):47–59
Everall I et al (2009) Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy. J Neuro-Oncol 15(5–6):360–370
Fritz-French C et al (2014) The recombinant vaccinia virus gene product, B18R, neutralizes interferon alpha and alleviates histopathological complications in an HIV encephalitis mouse model. J Interf Cytokine Res 34(7):510–517
Gorantla S, Poluektova L, Gendelman HE (2012) Rodent models for HIV-associated neurocognitive disorders. Trends Neurosci 35(3):197–208
Grant I et al (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 82(23):2055–2062
Griffin WC 3rd et al (2004) The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function. J Neuro-Oncol 10(2):109–115
Haile WB et al (2016) The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model. Neurobiol Dis 92(Pt B):137–143
Heaton RK et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: charter study. Neurology 75(23):2087–2096
Honeycutt JB et al (2015) Humanized mouse models for HIV-1 infection of the CNS. J Neuro-Oncol 21(3):301–309
Koneru R, Olive MF, Tyor WR (2014) Combined antiretroviral therapy reduces brain viral load and pathological features of HIV encephalitis in a mouse model. J Neuro-Oncol 20(1):9–17
Maki PM et al (2009) Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study. Neurology 72(19):1661–1668
Rao VR et al (2008) HIV-1 clade-specific differences in the induction of neuropathogenesis. J Neurosci 28(40):10010–10016
Rao VR et al (2013) Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology 10:61
Rumbaugh JA, Tyor W (2015) HIV-associated neurocognitive disorders: five new things. Neurol Clin Pract 5(3):224–231
Sas AR, Bimonte-Nelson HA, Tyor WR (2007) Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of interferon-alpha in the brain. AIDS 21(16):2151–2159
Sas AR et al (2009) Interferon-alpha causes neuronal dysfunction in encephalitis. J Neurosci 29(12):3948–3955
Tyor WR et al (1993) A model of human immunodeficiency virus encephalitis in scid mice. Proc Natl Acad Sci U S A 90(18):8658–8662
Villeneuve LM et al (2016) HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution. J Neuro-Oncol 22(5):564–574
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Tyor, W.R., Bimonte-Nelson, H. A mouse model of HIV-associated neurocognitive disorders: a brain-behavior approach to discover disease mechanisms and novel treatments. J. Neurovirol. 24, 180–184 (2018). https://doi.org/10.1007/s13365-017-0572-6
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DOI: https://doi.org/10.1007/s13365-017-0572-6