Selective Estrogen Receptor β Agonists: a Therapeutic Approach for HIV-1 Associated Neurocognitive Disorders

Kristen A. McLaurin, Landhing M. Moran, Rosemarie M. Booze, Charles F. Mactutus

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The persistence of HIV-1 associated neurocognitive disorders (HAND) in the post-cART era, afflicting between 40 and 70% of HIV-1 seropositive individuals, supports a critical need for the development of adjunctive therapeutic treatments. Selective estrogen receptor β agonists, including S-Equol (SE), have been implicated as potential therapeutic targets for the treatment of neurocognitive disorders. In the present study, the therapeutic efficacy of 0.2 mg SE for the treatment of HAND was assessed to address two key questions in the HIV-1 transgenic (Tg) rat. First, does SE exhibit robust therapeutic efficacy when treatment is initiated relatively early (i.e., between 2 and 3 months of age) in the course of viral protein exposure? Second, does the therapeutic utility of SE generalize across multiple neurocognitive domains? Treatment with SE enhanced preattentive processes and stimulus-response learning to the level of controls in all (i.e., 100%) HIV-1 Tg animals. For sustained and selective attention, statistically significant effects were not observed in the overall analyses (Control: Placebo, n = 10, SE, n = 10; HIV-1 Tg: Placebo, n = 10, SE, n = 10). However, given our a priori hypothesis, subsequent analyses were conducted, revealing enhanced sustained and selective attention, approximating controls, in a subset (i.e., 50%, n = 5 and 80%, n = 8, respectively) of HIV-1 Tg animals treated with SE. Thus, the therapeutic efficacy of SE is greater when treatment is initiated relatively early in the course of viral protein exposure and generalizes across neurocognitive domains, supporting an adjunctive therapeutic for HAND in the post-cART era. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)264-279
Number of pages16
JournalJournal of NeuroImmune Pharmacology
Volume15
Issue number2
DOIs
StatePublished - Jun 1 2020

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Keywords

  • Preattentive processes
  • S-Equol
  • Selective attention
  • Sustained attention

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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