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

Journal of Neuroinflammation

Dima A. Hammoud³  William C. Reid³  Dragan Maric¹  Michael Kassiou²  Elaine M. Jagoda⁴  Kristin L. Peterson³  Margaret R. Lentz³  Wael G. Ibrahim³  Xuyi Yue⁵  Dianne E. Lee³ 

[1] Division of Intermural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA;Chemistry Department, The University of Sydney, Sydney, Australia;Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda 20814-9692, MD, USA;Molecular Imaging Program (MIP), National Cancer Institute (NCI), Bethesda, MD, USA;Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA

关键词: Neuroinflammation;    Positron emission tomography;    Transgenic rat;    HIV;   

Others  :  1227054
DOI  :  10.1186/s12974-015-0390-9

 received in 2015-07-11, accepted in 2015-09-02,  发布年份 2015

【 摘 要 】

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 [ ¹⁸ F]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

[ ¹⁸ F]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. [ ¹⁸ F]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 [ ¹⁸ F]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.

【 授权许可】

   
2015 Lee et al.

【 图 表 】

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Figure 2.

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