Characterization of neuropathology in the HIV-1 transgenic rat at different ages

J Neuroimmunol. 2016 Mar 15:292:116-25. doi: 10.1016/j.jneuroim.2016.01.022. Epub 2016 Feb 3.

Abstract

The transgenic HIV-1 rat (Tg) is a commonly used neuroHIV model with documented neurologic/behavioral deficits. Using immunofluorescent staining of the Tg brain, we found astrocytic dysfunction/damage, as well as dopaminergic neuronal loss/dysfunction, both of which worsening significantly in the striatum with age. We saw mild microglial activation in young Tg brains, but this decreased with age. There were no differences in neurogenesis potential suggesting a neurodegenerative rather than a neurodevelopmental process. Gp120 CSF levels exceeded serum gp120 levels in some animals, suggesting local viral protein production in the brain. Further probing of the pathophysiology underlying astrocytic injury in this model is warranted.

Keywords: Astrocytic loss; HIV-1 transgenic rat; Neuro-HIV; Neuropathology; Neurotoxicity; Viral proteins.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • AIDS-Associated Nephropathy / metabolism
  • AIDS-Associated Nephropathy / pathology*
  • AIDS-Associated Nephropathy / virology*
  • Aging / pathology*
  • Animals
  • Brain / pathology*
  • Brain / virology
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • Calcium-Binding Proteins / metabolism
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Viral / physiology*
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • HIV Envelope Protein gp120 / cerebrospinal fluid
  • HIV Envelope Protein gp120 / genetics
  • HIV-1 / genetics
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Microfilament Proteins / metabolism
  • Rats
  • Rats, Transgenic
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Aif1 protein, rat
  • CD11b Antigen
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • HIV Envelope Protein gp120
  • Microfilament Proteins
  • Tyrosine 3-Monooxygenase