Lumbar spinal cord expression of Tollip, a Toll-like receptor pathway regulator in HIV Tat-associated sensory neuropathy
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B642
Abstract ID: 4314
Presenting Author:
Ling Cao , Professor at Univ. of New England
Abstract:
Using doxycycline inducible HIV-1 Tat transgenic (iTat) mice, we and others have shown that Tat induction is associated with HIV-sensory neuropathy (SN)-like behaviors. To further delineate the underlying mechanisms, we performed bioinformatic pathway analysis following a NanoString RNA assessment of 200+ inflammation-related genes in the lumbar spinal cord (LSC) of iTat mice. Four significant patterns of changes involving 38 genes across 3 major signaling pathways were identified: apoptosis, inflammation mediated by chemokines/cytokines, and TLR signaling. Nine of these genes were verified via qRT-PCR and showed significant time-dependent changes post-Tat induction. One gene, Tollip (Toll-interacting protein), is a key negative regulator of MyD88-dependent TLR pathway. We further examined Tollip’s cellular location in the LSC of iTat mice via IHC. Our results indicated that Tollip was not co-localized with LSC astrocytes (glial fibrillary acidic protein (GFAP)+) or microglia (CD11b+), but expressed in neurons (PGP9.5+ or NeuN+), specifically in tyrosine hydroxylase+ neurons. Although distributed throughout the LSC, Tollip+ cells appeared to be in higher abundance in the transition region between the dorsal and ventral horns of the LSC. Time course study showed consistent changes in Tollip expression at the protein level to that at the RNA level. Future work will identify potential sex-dependent Tollip expression and investigate the role of Tollip in Tat-associated HIV-SN.
Lumbar spinal cord expression of Tollip, a Toll-like receptor pathway regulator in HIV Tat-associated sensory neuropathy
Category
Poster and Podium (Block Symposium)