Biology subjects

Fields, J. A.

Publications and source records attributed to Fields, J. A..

2 recordsLinked to original sources

bioRxiv2026

Cannabis Use by People with HIV is Associated with an Anti-Inflammatory Immunometabolic Phenotype in Monocyte-Derived Macrophages

Chronic neuroinflammation is associated with comorbidities in people with HIV (PWH) on antiretroviral therapy (ART). While cannabis use is associated with reduced neuroinflammation and neurocognitive impairment (NCI) in PWH, the underlying mechanisms are unknown. To address this gap in knowledge, we analyzed monocyte-derived macrophages (MDMs) from a cohort of 50 PWH and 33 people without HIV (mean age: 61.9 years), categorized by frequency of cannabis use (naive/low, moderate, daily). We performed immunocytochemistry, RNA sequencing, and qPCR on MDMs and quantified related biomarkers in donor plasma. In this cohort study, daily cannabis use in PWH was associated with less global neurocognitive deficits, and with an anti-inflammatory immunometabolic-phenotype in MDMs characterized by (1) a metabolic shift from glycolysis to oxidative phosphorylation, (2) higher mitochondrial numbers, (3) altered cytokine profiles (pro-inflammatory downregulation, anti-inflammatory upregulation), and (4) higher brain-derived neurotrophic factor (BDNF) expression. These cellular changes were corroborated by a plasma biomarker profile in PWH including (1) lower levels of growth differentiation factor 15 and soluble triggering receptor expressed on myeloid cells 2, and (2) higher mature BDNF/precursor BDNF ratios that correlated with better cognition. Thus, cannabis use may mitigate NCI in PWH by immunometabolically reprogramming MDM function towards an anti-inflammatory and neuroprotective state. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/709579v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@15fb1adorg.highwire.dtl.DTLVardef@189d79corg.highwire.dtl.DTLVardef@aa6a89org.highwire.dtl.DTLVardef@3852f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Chronic nicotine treatment enhanced cognition and reduced neuroinflammation in the gp120 transgenic mouse model of neuroHIV

RationaleAntiretroviral development has improved the longevity of people with HIV (PWH), but many experience impaired cognition potentially due to neuroinflammation. PWH smoke cigarettes at higher rates than the general population, possibly for self-medication given cognitive-enhancing and anti-inflammatory properties of nicotine, the primary psychoactive ingredient cigarette smoke. We hypothesized that chronic nicotine would improve cognition in a mouse model of HIV, gp120 transgenic (Tg) mice, and reduce neuroinflammation. MethodsMale and female gp120-Tg mice (n=64) and littermate controls (n=67) were operantly trained then tested for effortful motivation in the progressive ratio breakpoint task (PRBT). Mice were counter-balanced into three groups for saline or nicotine minipump implantation (0, 14 or 40 mg/kg/day) then retested 25 days later in the PRBT, probabilistic reversal learning task (PRLT - reinforcement learning and cognitive flexibility), and Iowa Gambling Task (IGT - risk-based decision-making), with a subset tested for neuroinflammation (Iba-1 levels). ResultsGp120-Tg mice exhibited worse PRLT performance, attenuated by nicotine. Furthermore, nicotine selectively optimized their response strategies in the PRLT and IGT, increasing loss sensitivity, shifting animals towards "safer" responses. No motivation effects were observed. Nicotine also reduced Iba-1 expression, suggesting that its cognitive-enhancing effects may relate to reduced neuroinflammation. ConclusionGp120-Tg mice exhibited deficits in the PRLT, which are attenuated by chronic nicotine. Furthermore, nicotine improved reinforcement learning and risky decision-making supporting its therapeutic potential for cognitive deficits in PWH, possibly via reducing neuroinflammation. With potential negative consequences of long-term nicotine use, future studies should determine its mechanism of action to develop more targeted therapeutics.

neuroscience↗