Lack of neuroinflammation in the HIV-1 transgenic rat: An [18F]-DPA714 PET imaging study

Dianne E. Lee, Xuyi Yue, Wael G. Ibrahim, Margaret R. Lentz, Kristin L. Peterson, Elaine M. Jagoda, Michael Kassiou, Dragan Maric, William C. Reid, Dima A. Hammoud

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. Methods: Dynamic [18F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. Results: [18F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [18F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. Conclusion: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [18F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.

Original languageEnglish (US)
Article number171
JournalJournal of Neuroinflammation
Volume12
Issue number1
DOIs
StatePublished - Sep 17 2015

Keywords

  • HIV
  • Neuroinflammation
  • Positron emission tomography
  • Transgenic rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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