Brain, Behavior, and Immunity最新文献

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ + ) individuals have poorer mental and physical health than heterosexuals, and bisexuals fare worse than individuals who identify as lesbian and gay. However, data on stress biology among sexual minorities are critically insufficient. The current pilot study utilized data from 32 bisexual women - a subset of the National Couples' Health and Time Study - who completed questionnaires and provided blood samples to index biological aging from DNA methylation data (DunedinPACE, GrimAge2). The mean DunedinPACE score was 1.13 (SD = 0.18), which outpaced chronological aging by 13 % (p < 0.001). Likewise, bisexual women in this sample were, on average, 8.67 (SD = 5.96) years older biologically per GrimAge2 as compared to their chronological age. In covariate adjusted models, those reporting greater internalized homonegativity exhibited significantly greater epigenetic age acceleration (GrimAge2: p = 0.01; DunedinPACE: p = 0.041). Those who reported more frequent anti-bisexual experiences also showed accelerated GrimAge2 (p = 0.023). In contrast, those who reported stronger identity centrality (p = 0.017), stronger identity affirmation (p = 0.029), and more friend support (p = 0.018) - a critical type of support for LGBTQ + individuals - had slower GrimAge2. Depressive symptoms, anxiety and loneliness were not associated with GrimAge2 or DunedinPACE. Results suggest that bisexual women are at risk for accelerated aging, and those who have less internal and external affirmation of their sexual identity may be most at risk.

Spinal cord injuries (SCIs) impact between 250,000 and 500,000 people worldwide annually, often resulting from road accidents or falls. These injuries frequently lead to lasting disabilities, with the severity depending on the injury's extent and location. Emerging research also links SCIs to cognitive impairments due to brain inflammation. From a treatment perspective, various approaches, including cell therapy, have been investigated. One common mechanism across cellular transplant models is the modulation of inflammation at the injury site, though it remains uncertain if these effects extend to the brain. To explore this, we induced SCI in wild-type mice and treated them with either olfactory ensheathing cells or mesenchymal stem cells. Our findings reveal that both cell types can reverse SCI-induced cognitive deficits, reduce brain inflammation, and increase hippocampal neuronal density. This study is the first, to our knowledge, to demonstrate that cells transplanted into the spinal cord can influence brain inflammation and mitigate injury-induced effects on brain functions. These results highlight the intricate relationship between the spinal cord and brain in both health and disease.

Preclinical and clinical studies have established that autoreactive immunoglobulin G (IgG) can drive neuropathic pain. We recently demonstrated that sciatic nerve chronic constriction injury (CCI) in male and female mice results in the production of pronociceptive IgG, which accumulates around the lumbar region, including within the dorsal root ganglia (DRG) and spinal cord, facilitating the development of neuropathic pain. These data raise the intriguing possibility that neuropathic pain may be alleviated by reducing the accumulation of IgG. To this end, we tested whether biologic inhibition or genetic deletion of the neonatal Fc receptor (FcRn) would attenuate mechanical hypersensitivity (allodynia) and IgG deposition induced by CCI. FcRn are prominently expressed on myeloid and endothelial cells and extend the half-life of IgG via pinocytosis and recycling into the extracellular milieu. We show here that administration of the FcRn blocker efgartigimod either 7- or 28-days post-CCI relieved allodynia among both male and female mice, compared to the Fc fragment control. Efgartigimod, administered systemically (intraperitoneal) or to the lumbar region (intrathecal), attenuated mechanical allodynia for at least one month w. CCI-induced allodynia was similarly reduced in FcRn-deficient (FcRn^-) mice compared to wild-type mice. Biologic inhibition or genetic deletion of FcRn also reduced CCI-induced accumulation of IgG on macrophages and neurons in lumbar DRG, as well as microglia in the lumbar dorsal spinal cord. Expression of the Fc receptor γ subunit (FcRγ) was reduced in efgartigimod-treated or FcRn^- mice post-CCI compared to controls. The FcRγ subunit is a key component of Fc gamma receptors (FcγRs), which are activated by IgG immune complexes. In macrophage cultures stimulated by IgG immune complexes, FcRn blockade also dampened FcγR-dependent production of proinflammatory cytokines. Collectively, our study demonstrates that FcRn blockade or deletion alleviates mechanical allodynia and reduces IgG accumulation after CCI, attenuating pronociceptive IgG-FcγR signaling around the lumbar region. Strategies to block FcRn and reduce IgG recycling warrant further investigation as potential treatments for IgG-mediated neuropathic pain.

This study investigated the neural correlates of perceiving visual contagion cues characteristic of respiratory infections through functional magnetic resonance imaging (fMRI). Sixty-two participants (32f/ 30 m; ∼25 years on average) watched short videos depicting either contagious or non-contagious everyday situations, while their brain activation was continuously measured. We further measured the release of secretory immunoglobulin A (sIgA) in saliva to examine the first-line defensive response of the mucosal immune system. Perceiving sneezing and sick individuals compared to non-contagious individuals triggered increased activation in the anterior insula and other regions of the neuroimmune axis, that have been implicated in the somatosensory representation of the respiratory tract, and further led to increased release of sIgA. In line with predictions, this contagion cue-related activation of the insula was positively correlated with both perceived contagiousness and disgust evoked by the videos, as well as with the mucosal sIgA response. In contrast, the amygdala exhibited heightened activation to all videos featuring humans, regardless of explicit signs of contagion, indicating a nonspecific alertness to human presence. Nevertheless, amygdala activation was also correlated with the disgust ratings of each video. Collectively, these findings outline a neuroimmune mechanism for the processing of respiratory contagion cues. While the insula coordinates central and peripheral immune activation to match the perceived contagion threat, supposedly by triggering both increased sIgA release and contagion-related cognitions, the amygdala may rather act as an alerting system for social situations with a heightened transmission risk. This proactive neuroimmune response may help humans to manage contagion risks, that are difficult to avoid, by activating physiological and cognitive countermeasures in reaction to typical symptoms of respiratory infection, which prepares the organism for subsequent pathogen exposure.