Temporal relationships between HIV-1 Tat-induced neuronal degeneration, OX-42 immunoreactivity, reactive astrocytosis, and protein oxidation in the rat striatum

Michael Y. Aksenov, Ulla Hasselrot, Guanghan Wu, Avindra Nath, Carol Anderson, Charles F. Mactutus, Rosemarie M. Booze

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 transactivating protein Tat is neurotoxic and is believed to play a role in the development of AIDS-associated dementia complex. Neurotoxicity of Tat may be associated with oxidative stress. In this study we examined temporal progression of histopathological changes induced by a single microinjection of Tat 1-72 into the rat striatum. Degenerating neural cells, detected by Fluoro-Jade B staining and increased protein oxidation, determined by protein carbonyl immunostaining, were observed in the striatum as soon as 2 h following the microinjection. Further progression of neuronal degeneration was associated with pronounced infiltration of the area surrounding Tat 1-72 injection site by OX-42 positive macrophages/microglia, which was evident at the 24 h time point. Signs of reactive astrocytosis were found in the striatum of Tat 1-72 injected animals as late as 7 days following the single microinjection. Increased GFAP immunoreactivity and changes in the morphology of astrocytes coincided with a second phase of increased protein carbonyl formation, but not with neuronal degeneration. Control polypeptide, nontoxic Tat δ 31-61, did not cause any cell death, inflammatory reaction or oxidative damage. Results of our study support the hypothesis that oxidative stress may be an early step in the mechanism of Tat neurotoxicity.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalBrain research
Volume987
Issue number1
DOIs
StatePublished - Oct 10 2003

Keywords

  • HIV dementia
  • In vivo
  • Neurodegeneration
  • Striatum
  • Tat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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