Research Assistant University of New England north berwick, Maine, United States
Disclosure(s):
Samantha Willey: No financial relationships to disclose
Introduction/Rationale: HIV neuropathy is the most common neurological complication of HIV infection. We previously demonstrated that doxycycline inducible HIV Tat transgenic (iTat) mice display neuropathy-like behaviors following Tat induction. RNA profiling study via NanoString and qRT-PCR with the lumbar spinal cord of iTat mice indicated a Tat-induced upregulation of arachidonate 12-lipoxygenase (Alox 12) comparing to PBS-treated controls. Alox12 metabolizes arachidonic acid to generate proinflammatory lipid mediators. To further examine the role of Alox12 in Tat neuropathy, we assessed the expression of Alox12 in lumbar spinal cord at the protein level.
Methods: iTat mice were injected daily with doxycycline for 14 days to induce Tat expression. Lumbar spinal cord tissues were collected at days 0, 3, 7, 14, 21, 28, and 35 following Tat induction and processed for immunohistochemistry (IHC).
Results: Alox12 was found to be co-localized primarily with neuronal marker NeuN rather than astrocyte marker glial fibrillary acidic protein (GFAP) or microglial marker CD11b. Similar to RNA levels, Tat induced an increase in the number of Alox12+ cell within the spinal cord dorsal horn area that returned to baseline 35 days post the initiation of Tat induction. No sex differences were detected at this time.
Conclusion: Our current results support the potential contribution of Alox12-mediated inflammation to Tat-associated neuropathy-like behaviors.
