Journal
MOLECULAR BRAIN
Volume 4, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/1756-6606-4-23
Keywords
antiretrovirals; microglial cells; HIV; cognitive disorders
Categories
Funding
- Johnnie B. Byrd, Sr. Alzheimer's Center & Research Institute
- NIH/NIA/NIMH
Ask authors/readers for more resources
Up to 50% of long-term HIV infected patients, including those with systemically well-controlled infection, commonly experience memory problems and slowness, difficulties in concentration, planning, and multitasking. Deposition of A beta plaques is also a common pathological feature of HIV infection. However, it is not clear whether this accumulation is due to AD-like processes, HIV-associated immunosuppression, Tat protein-induced A beta elevations, and/or the effects of single highly active antiretroviral therapy (ART). Here we evaluated the effects of several ART medications (Zidovudine, Lamivudine, Indinavir, and Abacavir) alone and in combination on: 1) A beta(1-40), (42) generation in murine N2a cells transfected with the human Swedish mutant form of APP; 2) microglial phagocytosis of FITC-A beta(1-42) peptides in cultured murine N9 microglia. We report for the first time that these antiretroviral compounds (10 mu M) generally increase A beta generation (similar to 50-200%) in SweAPP N2a cells and markedly inhibit microglial phagocytosis of FITC-A beta(1-42) peptides in murine microglia. The most significant amyloidogenic effects were observed with combined ART (p < 0.05); suggesting certain ART medications may have additive amyloidogenic effects when combined. As these antiretroviral compounds are capable of penetrating the blood brain barrier and reaching the concentrations employed in the in vitro studies, these findings raise the possibility that ART may play a casual role in the elevated A beta found in the brains of those infected with HIV. Therefore these compounds may consequently contribute to cognitive decline observed in HIV associated neurocognitive disorders (HAND).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available