Open AccessA longitudinal characterization of sex-specific somatosensory and spatial memory deficits in HIV Tg26 heterozygous mice
Author(s) -
Mary F. Barbe,
Regina Loomis,
Adam M. Lepkowsky,
Steven D. Forman,
Huaqing Zhao,
Jennifer Gordon
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0244725
Subject(s) - morris water navigation task , barnes maze , neurocognitive , somatosensory system , medicine , neuroscience , physiology , psychology , hippocampus , spatial learning , cognition
The pathogenesis of human immunodeficiency virus associated neurological disorders is still not well understood, yet is known to result in neurological declines despite combination anti-retroviral therapy. HIV-1 transgenic (Tg26) mice contain integrated non-infectious HIV-1 proviral DNA. We sought to assess the integrity of neurocognitive function and sensory systems in HIV-1 Tg26 mice using a longitudinal design, in both sexes, to examine both age- and sex-related disease progression. General neurological reflexive testing showed only acclimation to repeated testing by all groups. Yet, at 2.5 months of age, female Tg26 +/- mice showed hyposensitivity to noxious hot temperatures, compared to wild types (both sexes) and male Tg26 +/- mice, that worsened by 10 months of age. Female Tg26 +/- mice had short-term spatial memory losses in novel object location memory testing at 2.5 and 7 months, compared to female wild types; changes not observed in male counterparts. Female Tg26 +/- mice showed mild learning deficits and short- and long-term spatial memory deficits in olfactory and visually cued Barnes Maze testing at 3 months of age, yet greater learning and memory deficits by 8 months. In contrast, male Tg26 +/- mice displayed no learning deficits and fewer spatial memory deficits (mainly heading errors in nontarget holes). Thus, greater sex-specific temperature hyposensitivity and spatial memory declines were observed in female HIV Tg26 +/- mice, than in male Tg26 +/- mice, or their wild type littermates, that increased with aging. Additionally, tibial bones were examined using ex vivo micro-CT after tissue collection at 11 months. Sex-dependent increases in bone volume and trabecular number were seen in males, matching their greater weights at this age. These results indicate that HIV-1 Tg26 mice is a promising model in which to study neuropathic mechanisms underlying peripheral pathology as well as cognitive deficits seen with HIV.