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Nicotine mediates expression of genes related to antioxidant capacity and oxidative stress response in HIV-1 transgenic rat brain

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Abstract

Oxidative stress plays an important role in the progression of HIV-1 infection. Nicotine can either protect neurons from neurodegeneration or induce oxidative stress, depending on its dose and degree of oxidative stress impairment. However, the relationship between nicotine and oxidative stress in the HIV-1-infected individuals remains largely unknown. The purpose of this study was to determine the effect of nicotine on expression of genes related to the glutathione (GSH)-centered antioxidant system and oxidative stress in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of HIV-1 transgenic (HIV-1Tg) and F344 control rats. Adult HIV-1Tg and F344 rats received nicotine (0.4 mg/kg, base, s.c.) or saline injections once per day for 27 days. At the end of treatment, various brain regions including the NAc and VTA were collected from each rat. Following total RNA extraction and complementary DNA (cDNA) synthesis of each sample, quantitative reverse transcription PCR (RT-PCR) analysis was performed for 43 oxidative-stress-related genes. Compared with F344 control rats, HIV-1Tg rats showed a significant downregulation of genes involved in ATPase and cyctochrome oxidase at the messenger RNA (mRNA) level in both regions. Further, we found a significant downregulation of Gstm5 in the NAc and upregulation of Cox1, Cox3, and Gsta6 in the VTA of HIV-1Tg rats. HIV-1Tg rats showed brain-region-specific responses to chronic nicotine treatment. This response resulted in a change in the expression of genes involved in antioxidant mechanisms including the downregulation of genes such as Atp5h, Calml1, Gpx7, Gstm5, Gsr, and Gsta6 and upregulation of Sod1 in the NAc, as well as downregulation of genes like Cox5a, Gpx4, Gpx6, Gpx7, Gstm5, and Sod1 in the VTA of HIV-1Tg rats. Together, we conclude that chronic nicotine treatment has a dual effect on the antioxidant defense system and oxidative-stress-induced apoptosis signaling in HIV-1Tg rats. These findings suggest that nicotine has a negative effect on response to oxidative stress and antioxidant processes in HIV-1 Tg rat brain, especially in the VTA.

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Acknowledgments

The project was supported, in part, by US National Institutes of Health grants DA-012844 to MDL, DA-016149 to SLC, and DA-026356 to SLC and MDL.

Conflict of interest

The authors declare no conflict of interest with the study or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 450 Ray C Hunt Drive, Suite G-170, Charlottesville, VA, 22903, USA

    Guohua Song, Tanseli Nesil, Junran Cao & Ming D. Li

  2. Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, China

    Guohua Song

  3. Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA

    Zhongli Yang & Sulie L. Chang

  4. Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA

    Sulie L. Chang

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  1. Guohua Song
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  2. Tanseli Nesil
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  6. Ming D. Li
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Correspondence to Ming D. Li.

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Song, G., Nesil, T., Cao, J. et al. Nicotine mediates expression of genes related to antioxidant capacity and oxidative stress response in HIV-1 transgenic rat brain. J. Neurovirol. 22, 114–124 (2016). https://doi.org/10.1007/s13365-015-0375-6

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  • DOI: https://doi.org/10.1007/s13365-015-0375-6

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