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Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats

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Abstract

Binge drinking affects the onset and progression of human immunodeficiency virus (HIV)-associated neurological disorders. The HIV-1 transgenic (HIV-1Tg) rat was created with a gag- and pol-deleted HIV-1 viral genome to mimic HIV-infected patients receiving combination anti-retroviral therapy (cART). Docosahexaenoic acid (DHA) is a marine compound that modulates inflammatory responses. Using HIV-1Tg rats subjected to binge exposure to ethanol (EtOH), this study examined whether DHA could reduce the detrimental neurological effects of EtOH and HIV proteins. Young adult male HIV-1Tg and F344 control rats received 4 mL/kg/day saline as a control (Saline group), 20 mg/kg/day DHA (DHA group), 4.8 g/kg/day 52% w/v EtOH (EtOH group), or 4.8 g/kg/day 52% w/v EtOH and 20 mg/kg/d DHA (DHA + EtOH group) by gavage for 5 weeks (n = 6 per group). EtOH was administrated on days 5, 6, and 7 of each week. Locomotor activity (LMA) was assessed using open field tests before and 45, 90, 135, and 180 min after each treatment. Repeated binge EtOH exposure gradually decreased LMA measured before daily treatments in HIV-1Tg and F344 rats, an effect that was reversed by DHA only in the HIV-1Tg rats. Decreased LMA of rats after treatment and under the influence of EtOH was less pronounced, and the reversal effect of DHA did not reach statistical significance. The plasma endotoxin level was significantly higher in HIV-1Tg rats than in F344 rats. IL-6 and IL-18 expression in the striatum was significantly higher in the HIV-1Tg EtOH group than in the F344 EtOH group. DHA significantly decreased the high levels of IL-6, IL-18, and NF-κB expression observed in the HIV-1Tg EtOH group. DHA appears to ameliorate inflammation and consequently lessen the reductions in LMA produced by the combination of EtOH and HIV-1 viral proteins.

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Acknowledgements

This work was partially supported by the National Institutes of Health (NIH) grants AA023172 and DA036175 to Sulie L. Chang, as well as the Oversea Study Fellowship from the China Scholarship Council to Jianlin He, No. 201400100091. We thank Andrew Dieterich for his dedication to the animal care.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China

    Jianlin He & Shizhong Zheng

  2. Institute of NeuroImmune Pharmacology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ, 07079, USA

    Jianlin He, Wenfei Huang, Michael Vigorito & Sulie L. Chang

  3. State Oceanic Administration, Third Institute of Oceanography, Xiamen, 361005, People’s Republic of China

    Jianlin He

  4. Department of Biological Sciences, Seton Hall University, South Orange, NJ, 07079, USA

    Wenfei Huang & Sulie L. Chang

  5. Department of Psychology, Seton Hall University, South Orange, NJ, 07079, USA

    Michael Vigorito

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  1. Jianlin He
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Contributions

SLC and JH conceived and designed the experiments. JH and WH performed the lab work. SLC provided experimental animals/reagents/materials/analysis tools. JH, WH, MV, and SLC analyzed the data. JH, WH, SZ, MV, and SLC wrote the manuscript.

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Correspondence to Shizhong Zheng or Sulie L. Chang.

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The experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) at Seton Hall University, South Orange, NJ.

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The authors declare that they have no conflicts of interest.

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He, J., Huang, W., Zheng, S. et al. Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats. J. Neurovirol. 24, 88–97 (2018). https://doi.org/10.1007/s13365-017-0597-x

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