It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/G signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages.

Objectives:Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition.Participants:154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included.Measurements:Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures.Results:Frailty severity predicted weaker executive function (B = −2.77, β = −0.30, 95% CI = −4.05 – −1.29) and processing speed (B = −1.57, β = −0.17, 95% CI = −3.10 – −0.16). Poor sleep quality predicted poorer executive function (B = −0.47, β = −0.21, 95% CI = −0.79 – −0.08), processing speed (B = −0.64, β = −0.28, 95% CI = −0.98 – −0.31), learning (B = −0.42, β = −0.19, 95% CI = −0.76 – −0.05) and delayed recall (B = −0.41, β = −0.16, 95% CI = −0.80 – −0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = −0.66, β = −0.07, 95% CI = −1.48 – −0.39), learning (B = −0.85, β = −0.07, 95% CI = −1.85 – −0.12), delayed recall (B = −0.47, β = −0.08, 95% CI = −2.12 – −0.39) and processing speed (B = −0.90, β = −0.09, 95% CI = −1.85 – −0.20).Conclusions:Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.

Both HIV disease and frailty syndrome are risk factors for neurocognitive impairment. Longitudinal research among individuals of the general population suggests that frailty predicts future cognitive decline; however, there is limited evidence for these longitudinal relationships among people living with HIV (PLWH). The current study evaluated and compared rates of cognitive decline over 2 years among HIV serostatus and frailty status groups. Participants included 50 PLWH and 60 HIV-uninfected (HIV−) participants who were evaluated at baseline and 2-year follow-up visits. Baseline frailty status (non-frail, pre-frail, and frail) was determined using fried frailty phenotype criteria. Neurocognitive functioning was measured using practice-effect corrected scaled scores derived from a comprehensive neuropsychological battery covering seven cognitive domains. Repeated measures analysis was used to estimate rates of global and domain-specific cognitive change from baseline to 2-year follow-up among each of six HIV/frailty status groups. Among PLWH, the pre-frail group demonstrated consistent declines in global cognitive functioning (B = − 0.029, p = 0.034), processing speed (B = − 0.047, p = 0.031), and motor functioning (B = − 0.048, p = 0.038). Among HIV− participants, pre-frail individuals also declined in global cognitive functioning and processing speed (ps ≤ 0.05). HIV− non-frail participants also declined in the cognitive domains of learning, delayed recall, and motor functioning; however, these declines appeared to be driven by relatively higher baseline scores among this group. Notably, 38% of PLWH changed in frailty status from baseline to follow-up, and those with stable pre-frailty demonstrated higher likelihood for cognitive decline; change in depressive symptoms did not relate to change in frailty status. Current findings highlight pre-frailty as an important clinical syndrome that may be predictive of cognitive decline among PLWH. Interventions to prevent or reduce frailty among vulnerable PLWH are needed to maintain optimal cognitive health.

Background: Even in the era of suppressive antiretroviral therapy, people with HIV (PWH) suffer greater exposure to inflammation than their uninfected peers. Although poor social support and social isolation have been linked to systemic inflammation in the general population, it is not known whether this is true also among PWH. Methods: People with and without HIV infection were enrolled in a community-based, single-center study. Primary predictors were the Medical Outcomes Study Social Support Survey, and outcomes were a panel of inflammatory biomarkers (ICAM-1, MCP-1, IL-6, IL-8, IP-10, C-reactive protein, D-dimer, VEGF, sCD14, and uPAR) in blood plasma and cerebrospinal fluid (CSF). Results: PWH had worse positive social support (P = 0.0138) and affectionate support (P = 0.0078) than did HIV− individuals. A factor analysis was used to group the biomarkers into related categories separately for each fluid. Levels of 3 of the 4 plasma factors were significantly higher in PWH than HIV− (ps = 0.007, 0.001, and 0.0005, respectively). Levels of 1 of the 3 CSF factors also were significantly higher in PWH than HIV− (P = 0.0194). In the combined PWH and HIV− cohort, poorer social support was associated with higher levels of a factor in plasma loading on MCP-1, IL-8, and VEGF (P = 0.020) and with a CSF factor loading on MCP-1 and IL-6 (P = 0.006). Conclusion: These results suggest that enhancing social support might be an intervention to reduce inflammation and its associated adverse outcomes among PWH.

Objective:Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.Methods:263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.Results:HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).Conclusions:Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.