AUTHOR=Bertrand Sarah , Hu Calvin , Aksenova Marina , Mactutus Charles , Booze Rosemarie 

TITLE=HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 6 - 2015

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00894

DOI=10.3389/fmicb.2015.00894

ISSN=1664-302X

ABSTRACT=Illicit drugs, such as cocaine, are known to increase the likelihood and severity of HIV-1 associated neurocognitive disorders (HAND). In the current studies synaptic integrity was assessed following exposure to low concentrations of the HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines) on neuronal dendrites in vitro. In addition, the synapse-protective effects of either R-Equol or S-Equol (derivatives of the soy isoflavone, daidzein) were determined. Individually, neither low concentrations of HIV-1 Tat (10nM) nor low concentrations of cocaine (1.6µM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat+cocaine together significantly reduced dendritic synapses. This synaptic reduction was prevented by pre-treatment with either R-Equol or S-Equol, in an estrogen receptor beta (ERβ) dependent manner. In sum, targeted therapeutic intervention with S-Equol may prevent HIV-1+drug abuse synaptopathy, and thereby potentially delay the development of HAND.