Phenotype of lumbar spinal cord Tollip+ cells in HIV Tat-associated peripheral neuropathy, a potential new role of tyrosine hydroxylase positive neurons 2657

Abstract Description HIV-associated peripheral neuropathy (HIV-PN) is a frequent complication of HIV infection with limited treatment options. Studies with doxycycline-inducible HIV-1 trans-activator of transcription (Tat) transgenic (iTat) mice suggest Tat contributes to the development of HIV-PN. We previously observed a transient increase in Toll-interacting protein (Tollip) RNA expression in the lumbar spinal cord (LSC) in iTat mice post-Tat induction and a significant overlap of Tollip+ cells with tyrosine hydroxylase (TH)+ neurons (catecholaminergic neurons) within the LSC. We phenotyped LSC Tollip+ cells in iTat mice via immunohistochemistry on several related markers: aromatic acid decarboxylase (AADC), vesicular monoamine transporter isoform 2 (VMAT2), and dopamine beta-hydroxylase (DBH). In naïve iTat mice, ∼90% of LSC Tollip+ cells expressed TH, decreasing slightly to ∼70% 21 days post-Tat induction. Tollip+ cells were rarely AADC + (<0.5%) while near 20% of Tollip+ cells were VMAT2+. This suggests LSC Tollip+ cells are not classical catecholaminergic neurons (TH+AADC+VMAT2+). They are likely either dopaergic neurons (TH+AADC-VMAT2-) or a population of TH+ neurons (TH+AADC-VMAT2+) that has not been reported in spinal cord. In addition, a significant proportion (∼30%) of Tollip+ cells co-expressed DBH. No significant sex differences in any of the markers are noted at this time. Functional involvement of LSC Tollip+TH+ neurons in HIV-PN will be investigated in the future. Funding Sources Supported by NIH/NINDS 1R01NS132674 (PI Cao). Topic Categories Immune Mechanisms of Human Disease (HUM)