Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats

Yang, Zhongli; Nesil, Tanseli; Connaghan, Kaitlyn P.; Li, Ming D.; Chang, Sulie L.

doi:10.1007/s11481-016-9679-4

Cited by 20 publications

(12 citation statements)

References 46 publications

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“…This is also in line with previous reports of dopaminergic dysfunction in the Tg rats ( Webb et al, 2010 , Moran et al, 2013b , Moran et al, 2012 , Silvers et al, 2007 ) which probably parallels known susceptibility of the dopaminergic system to HIV in infected patients ( Kumar et al, 2011 , Kumar et al, 2009 , Chang et al, 2008 , Gelman et al, 2006 ). It again draws attention to the compounding effects of addiction drugs on a system that is already compromised, with worse damage seen in the Tg rats compared to WT rats under the effect of nicotine ( Yang et al, 2017 , Yang et al, 2016 , Song et al, 2016 , Cao et al, 2016 , Nesil et al, 2015 ), ethanol ( Wingo et al, 2016 , Sarkar et al, 2013 ), methamphetamine ( Moran et al, 2012 , Pang et al, 2013 , Henry et al, 2013 , Kass et al, 2010 , Liu et al, 2009 ) or cocaine administration ( Moran et al, 2013b , McIntosh et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat

Casas

Muthusamy

Wakim

et al. 2018

NeuroImage: Clinical

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IntroductionHIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients.Materials and methodsCross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits.ResultsCross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats.ConclusionThe disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

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Section: Discussionmentioning

confidence: 99%

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat

Casas

Muthusamy

Wakim

et al. 2018

NeuroImage: Clinical

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“…Previous studies of the effects of nicotine in the HIV1Tg rat model suggest that chronic nicotine exposure can have region-specific effects on nicotine-sensitive areas of brain (Song et al 2016; Yang et al 2016). In the studies reported here, where the rats were exposed to nicotine at a slightly higher dose and for a longer duration, as well as to potentially additional stress from behavioral and motor testing, we observed that TNF-α, IL-1, and IL-6 gene expression levels were all increased by smoke exposure in HIV1Tg rat brains, whereas IL-6 gene expression was not increased by the exposures in F344 rat brains, suggesting the existence of a greater susceptibility to such exposures for the transgenic rat.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke and nicotine effects on brain proinflammatory responses and behavioral and motor function in HIV-1 transgenic rats

et al. 2018

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Cognitive impairment in HIV-1 infection is associated with the induction of chronic proinflammatory responses in the brains of infected individuals. The risk of HIV-related cognitive impairment is increased by cigarette smoking, which induces brain inflammation in rodent models. To better understand the role of smoking and the associated immune response on behavioral and motor function in HIV infection, wild-type F344 and HIV-1 transgenic (HIV1Tg) rats were exposed to either smoke from nicotine-containing (regular) cigarettes, smoke from nicotine-free cigarettes, or to nicotine alone. The animals were then tested using the rotarod test (RRT), the novel object recognition test (NORT), and the open field test (OFT). Subsequently, brain frontal cortex from the rats was analyzed for levels of TNF-α, IL-1, and IL-6. On the RRT, impairment was noted for F344 rats exposed to either nicotine-free cigarette smoke or nicotine alone and for F344 and HIV1Tg rats exposed to regular cigarette smoke. Effects from the exposures on the OFT were seen only for HIV1Tg rats, for which function was worse following exposure to regular cigarette smoke as compared to exposure to nicotine alone. Expression levels for all three cytokines were overall higher for HIV1Tg than for F344 rats. For HIV1Tg rats, TNF-α, IL-1, and IL-6 gene expression levels for all exposure groups were higher than for control rats. All F344 rat exposure groups also showed significantly increased TNF-α expression levels. However, for F344 rats, IL-1 expression levels were higher only for rats exposed to nicotine-free and nicotine-containing CS, and no increase in IL-6 gene expression was noted with any of the exposures as compared to controls. These studies, therefore, demonstrate that F344 and HIV1Tg rats show differential behavioral and immune effects from these exposures. These effects may potentially reflect differences in the responsiveness of the various brain regions in the two animal species as well as the result of direct toxicity mediated by the proinflammatory cytokines that are produced by HIV proteins and by other factors that are present in regular cigarette smoke.

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“…Nicotine and nicotinic receptors are involved in the modulation of innate immune pathways (Cui and Li 2010). To understand nicotine’s immunomodulation effects in HIV-1Tg rats, 52 immune-related genes were examined in three brain regions (PFC, NAc, and VTA) with or without nicotine treatment (Yang et al 2016). The pharmacological effect of nicotine on the expression of immune-related genes differed in the presence (HIV-1Tg rats) and absence (control F344 rats) of HIV-1 viral proteins.…”

Section: Nicotine’s Neuroprotective Effects Against Hiv/aidsmentioning

confidence: 99%

Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

Han

Yang

Chang

et al. 2018

J Neuroimmune Pharmacol

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Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative and positive pharmacological effects of nicotine have been shown in numerous animals and human studies, its interaction with human immunodeficiency virus-1 (HIV-1) have not been fully elucidated. Even though combined anti-retroviral therapy (cART) limits the progression of HIV-1 to acquired immune deficiency syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent. There is thus a compelling need to enhance our understanding of HAND-related neurologic dysfunction. Some biochemical pathways and physiological dysfunctions have been found to be shared by HAND and Alzheimer's (AD) or Parkinson's (PD) diseases, and nicotine may exert the same neuroprotection in HAND that has been observed in both AD and PD. In the past dozen years, various potential therapeutic effects of nicotine such as neuroprotection have been revealed in both in vivo and in vitro studies, including using HIV-1 transgenic (HIV-1Tg) rat model, which mimics HIV-infected patients receiving cART. In the current review, we describe recent progress in the prevalence of HIV/AIDS with and without cigarette smoking, some animal models for studying neural dysfunction associated with HIV-1 infection, elucidating the modulatory effects of cigarette smoking/nicotine on HIV/AIDS, the anti-inflammatory effects of nicotine, and the neuroprotective effects observed in HIV-1Tg rat model. Taken together, these findings suggest the following: although tobacco smoking does cause deleterious effects in both health and disease conditions such as HIV infection, nicotine, the significant component of tobacco smoke, has been shown to possess some neuroprotective effects in HIV patients, possible via its anti-inflammatory activities. It is therefore necessary to study nicotine's dual effects on neuroHIV/neuroAIDS in hope of better defining the potential medical uses of nicotine or its analogues, and to make them available in a purer and less dangerous form.

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Modulation Effect of HIV-1 Viral Proteins and Nicotine on Expression of the Immune-Related Genes in Brain of the HIV-1 Transgenic Rats

Cited by 20 publications

References 46 publications

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat

Cigarette smoke and nicotine effects on brain proinflammatory responses and behavioral and motor function in HIV-1 transgenic rats

Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

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