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Age-Related Decrease in Tyrosine Hydroxylase Immunoreactivity in the Substantia Nigra and Region-Specific Changes in Microglia Morphology in HIV-1 Tg Rats

  • David R. Goulding
  • Andrew Kraft
  • Peter R. Mouton
  • Christopher A. McPherson
  • Valeria Avdoshina
  • Italo Mocchetti
  • G. Jean HarryEmail author
Original Article
  • 59 Downloads

Abstract

Animal models have been used to study cellular processes related to human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorders (HAND). The HIV-1 transgenic (Tg) rat expresses HIV viral genes except the gag-pol replication genes and exhibits neuropathological features similar to HIV patients receiving combined antiretroviral therapy (cART). Using this rat, alterations in dopaminergic function have been demonstrated; however, the data for neuroinflammation and glial reactivity is conflicting. Differences in behavior, tyrosine hydroxylase (TH) immunoreactivity, neuroinflammation, and glia reactivity were assessed in HIV-1 Tg male rats. At 6 and 12 weeks of age, rotarod performance was diminished, motor activity was not altered, and active avoidance latency performance and memory were diminished in HIV-1 Tg rats. TH+ immunoreactivity in the substantia nigra (SN) was decreased at 8 months but not at 2–5 months. At 5 months, astrocyte and microglia morphology was not altered in the cortex, hippocampus, or SN. In the striatum, astrocytes were unaltered, microglia displayed slightly thickened proximal processes, mRNA levels for Iba1 and Cd11b were elevated, and interleukin (Il)1α,Cxcr3, and cell adhesion molecule, Icam, decreased. In the hippocampus, mRNA levels for Tnfa and Cd11b were slightly elevated. No changes were observed in the cortex or SN. The data support an age-related effect of HIV proteins upon the nigrostriatal dopaminergic system and suggest an early response of microglia in the terminal synaptic region with little evidence of an associated neuroinflammatory response across brain regions.

Keywords

HAND HIV Rotarod Dopamine Microglia Hippocampus Astrocyte Neuroinflammation Learning 

Notes

Funding Information

This work was supported in part by HHS grants NS079172 and NS074916 to IM and NIH intramural research funding Z01 ES021164-12 and Z01 ES101623-05 to JH.

Compliance with Ethical Standards

Animal studies were done in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals following approved animal protocols from the Animal Care and Use Committee of the National Institute of Environmental Health Sciences.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_77_MOESM1_ESM.pdf (6 mb)
ESM 1 (PDF 6097 kb)

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©  This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2019

Authors and Affiliations

  1. 1.Comparative Medicine BranchNational Institute of Environmental Health SciencesResearch Triangle ParkUSA
  2. 2.National Toxicology Program LaboratoryNational Institute of Environmental Health Sciences (NIEHS)Research Triangle ParkUSA
  3. 3.U.S. Environmental Protection Agency HeadquartersWashingtonUSA
  4. 4.SRC BiosciencesTampaUSA
  5. 5.Laboratory of Preclinical Neurobiology, Department of NeuroscienceGeorgetown UniversityWashingtonUSA

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