Back to Search
Start Over
Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders
- Source :
- Journal of Neuropathology & Experimental Neurology. 74:1093-1118
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals suffer from HIV-Associated Neurocognitive Disorders (HAND). Studies of antiretroviral treated patients have revealed persistent white matter pathologies including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction as the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors Ritonavir or Lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed following drug removal. Conversely, nucleoside reverse transcriptase inhibitor Zidovudine had no effect. Furthermore, in vivo Ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity, and have implications for myelination in juvenile HIV patients, and myelin maintenance in adults on lifelong therapy.
- Subjects :
- Adult
Gene Expression Regulation, Viral
Male
Pediatric AIDS
HIV Infections
Article
Pathology and Forensic Medicine
Cohort Studies
White matter
Mice
Cellular and Molecular Neuroscience
Myelin
Gangliosides
medicine
Animals
Humans
Myelin Proteolipid Protein
Cells, Cultured
Myelin Sheath
biology
virus diseases
Cell Differentiation
Myelin Basic Protein
General Medicine
Middle Aged
Oligodendrocyte
Myelin proteolipid protein
Myelin basic protein
Mice, Inbred C57BL
Disease Models, Animal
Oligodendroglia
medicine.anatomical_structure
Animals, Newborn
nervous system
Neurology
Myelin maintenance
Antirheumatic Agents
Immunology
biology.protein
Ritonavir
Neurology (clinical)
Cognition Disorders
Reactive Oxygen Species
medicine.drug
Subjects
Details
- ISSN :
- 15546578 and 00223069
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Journal of Neuropathology & Experimental Neurology
- Accession number :
- edsair.doi.dedup.....1bbeddcfed41d8032d6d59357fdd6470