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Publication Abstract Display
Type: Poster
Title: Reduced Δ5-ADIOL in CSF and Plasma as a Biomarker of Neurocognitive Impairment in HIV Infection.
Authors: Saijo K, Moore D, Gouaux B, Grant I, Ellis R
Date: 03-16-2013
Abstract:Background: Microglial activation and related inflammatory responses have been demonstrated in HIV-associated neurocognitive impairment (NCI) and may play a role in neuropathogenesis, even after combination antiretroviral therapies (cART) produce successful viral suppression and immune recovery. We evaluated a recently discovered pathway by which microglial inflammatory responses are downregulated , through binding of the endogenous neurosteroid 5-ANDROSTEN-3β, 17β-DIOL (Δ5-ADIOL) to the estrogen receptor (ER)β . Objective: To determine whether plasma and CSF levels of Δ5-ADIOL are reduced in HIV+ with NCI. Methods: Participants: 10 HIV+ (5 with NCI); 5 healthy, HIV seronegative (HIV-) controls matched by gender (100% men), age (mean, 42.2) and education (mean 12.5). All HIV+ were receiving cART and virologically suppressed. Participants underwent lumbar puncture, phlebotomy and detailed medical, neurological and neurocognitive examinations. Neurosteroids were extracted from cerebrospinal fluid (CSF) and plasma and quantitated by enzyme Immunoassay (EIA). Results: Levels of ADIOL in CSF were on average 6-fold higher than in plasma. Compared to HIV- individuals (CSF, 1289.7±374.6; plasma, 215.4 ± 263.1) and to HIV+ unimpaired subjects (CSF, 1010.7 ±450.3; plasma, 38.9 ±44.3) CSF ADIOL was decreased in impaired HIV+ subjects both in CSF (507.2 ± 188.1, p < 0.01) and plasma (5.9 ± 4.3). Conclusions: CSF Δ5-ADIOL levels were reduced in HIV+ NCI participants. Since the expression of HSD17B14 is down-regulated by inflammation and up-regulated by the anti-inflammatory cytokine interleukin, (IL)-10, Δ5-ADIOL levels in CSF might be used as a biomarker for neuroinflammation in HIV. If confirmed, these results open the possibility of preclinical and clinical studies on exogenous ER beta ligands as potential interventions for HIV NCI.

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