Biology subjects

Rademacher, L.

Publications and source records attributed to Rademacher, L..

7 recordsLinked to original sources

bioRxiv2026

Interleukin-6 responses to acute stress are not altered in alcohol use disorder despite elevated baseline inflammation

Acute stress activates the immune system, leading to the release of pro-inflammatory cytokines, such as interleukin-6 (IL-6). Chronic alcohol consumption alters the physiological stress systems and is associated with increased chronic inflammation. However, it remains unclear how IL-6 responds to acute stress in individuals with alcohol use disorder (AUD). Forty patients with AUD during early abstinence and 37 healthy controls (HC) completed two study visits. On one day, an acute stress induction task was performed, and on the other, a non-stressful control task, with the order of tasks being balanced. Plasma IL-6 and C-reactive protein (CRP) were measured as inflammatory markers at baseline and changes in IL-6 were assessed 90 minutes after the experimental manipulation. Patients with AUD showed significantly elevated baseline IL-6 and CRP compared to HC and the levels correlated positively with the amount of consumed alcohol in patients. IL-6 responses to the stress intervention did not differ between groups. Increases in IL-6 were observed on stress and control days and were larger when samples were collected via an indwelling catheter than with a butterfly needle. These findings suggest that IL-6 responses to acute stress do not differ between AUD and HC, despite increased baseline inflammation. Furthermore, the results indicate that blood collection methods can influence IL-6 measurements and highlight the importance of methodological considerations.

immunology↗

bioRxiv2025

No neurobehavioral evidence for reduced motivational potential of social rewards in alcohol use disorder

BackgroundThe mesolimbic dopamine system plays a central role in motivating behavior. In alcohol use disorder (AUD), this system is thought to be dysfunctional, leading to hyperreactivity to alcohol-related cues. In contrast, evidence on how individuals with AUD respond to alcohol-unrelated reward cues is inconclusive, and the motivation for social rewards has not yet been investigated. MethodsTo address this gap, 36 individuals with AUD and 34 healthy controls performed an incentive delay task to assess social reward anticipation with a monetary and a non-reward control condition while undergoing functional magnetic resonance imaging. The ventral striatum was defined as region of interest because of its central role in neuronal circuits for motivation. ResultsNeither behavioral nor neuroimaging data provided any evidence of reduced motivation for social or monetary rewards in AUD. Exploratory whole-brain analyses only revealed stronger activation in the occipital/cuneal cortex in individuals with AUD than in healthy controls across all trials. ConclusionTogether, these results suggest that sensitivity to social reward cues is not fundamentally impaired in AUD. Furthermore, they imply that motivational changes related to the substance do not generally alter the reward potential of alcohol-unrelated domains in AUD, opening perspectives for social-behavioral treatments for this disorder.

neuroscience↗

bioRxiv2024

Cell non-autonomous signaling through the conserved C. elegans glycopeptide hormone receptor FSHR-1 regulates cholinergic neurotransmission

Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored. Glycoproteins and their G protein-coupled receptors (GPCRs) are well-established orchestrators of multi-tissue signaling events that govern diverse physiological processes through both cell-autonomous and cell non-autonomous regulation. Here, we show that follicle stimulating hormone receptor, FSHR-1, the sole Caenorhabditis elegans ortholog of mammalian glycoprotein hormone GPCRs, is important for cell non-autonomous modulation of synaptic transmission. Inhibition of fshr-1 expression reduces muscle contraction and leads to synaptic vesicle accumulation in cholinergic motor neurons. The neuromuscular and locomotor defects in fshr-1 loss-of-function mutants are associated with an underlying accumulation of synaptic vesicles, build-up of the synaptic vesicle priming factor UNC-10/RIM, and decreased synaptic vesicle release from cholinergic motor neurons. Restoration of FSHR-1 to the intestine is sufficient to restore neuromuscular activity and synaptic vesicle localization to fshr-1-deficient animals. Intestine-specific knockdown of FSHR-1 reduces neuromuscular function, indicating FSHR-1 is both necessary and sufficient in the intestine for its neuromuscular effects. Re-expression of FSHR-1 in other sites of endogenous expression, including glial cells and neurons, also restored some neuromuscular deficits, indicating potential cross-tissue regulation from these tissues as well. Genetic interaction studies provide evidence that downstream effectors gsa-1/GS, acy-1/adenylyl cyclase and sphk-1/sphingosine kinase and glycoprotein hormone subunit orthologs, GPLA-1/GPA2 and GPLB-1/GPB5, are important for FSHR-1 modulation of the NMJ. Together, our results demonstrate that FSHR-1 modulation directs inter-tissue signaling systems, which promote synaptic vesicle release at neuromuscular synapses.

neuroscience↗

bioRxiv2024

Altered physiological, affective, and functional connectivity responses to acute stress in patients with alcohol use disorder

BackgroundThere is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The present study examined physiological and affective responses to stress and functional connectivity in AUD. MethodsSalivary cortisol samples, pulse rate, and affect ratings were collected on two days from 34 individuals with moderate or severe AUD and 34 controls. On one day, stress was induced, and on the other day, a non-stressful control task was performed. Following the intervention, participants underwent fMRI to assess functional connectivity, focusing on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. ResultsFor pulse rate and cortisol, stress responses were blunted in AUD, whereas negative affect was increased. Furthermore, stress-related changes in pulse rate, cortisol, and affect were only correlated in healthy controls. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior DMN, cerebellum and midcingulate cortex, and of the posterior DMN seed with the striatum and thalamus. ConclusionsThe results suggest a dissociation between subjective experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies.

neuroscience↗

bioRxiv2021

Association of stress-related limbic activity and baseline interleukin-6 plasma levels in healthy adults

Several studies suggest a link between acute changes in inflammatory parameters due to an endotoxin or (psychological) stressor and the brains stress response. The extent to which basal circulating levels of inflammatory markers are associated with the brains stress response has been hardly investigated so far. In the present study, baseline plasma levels of the cytokine interleukin (IL)-6 were obtained and linked to neural markers of psychosocial stress using a modified version of the Montreal Imaging Stress Task in a sample of N=65 healthy subjects (N=39 female). Of three a-priori defined regions of interest - the amygdala, anterior insula, and anterior cingulate cortex - baseline IL-6 was significantly and negatively associated with stress-related neural activation in the right amygdala and left anterior insula. Our results suggest that baseline cytokines might be related to differences in the neural stress response and that this relationship could be inverse to that previously reported for induced acute changes in inflammation markers.

neuroscience↗

bioRxiv2020

Self-beneficial belief updating as a coping mechanism for stress-induced negative affect

Being confronted with social-evaluative stress elicits a physiological and a psychological stress response. This calls for regulatory processes to manage negative affect and maintain self-related optimistic beliefs. The aim of the current study was to investigate the affect-regulating potential of self-related belief updating after exposure to social-evaluative stress, in comparison to non-social physical stress or no stress. We assessed self-related belief updating using trial-by-trial performance feedback and described the updating behavior in a mechanistic way using computational modeling. We found that social-evaluative stress was accompanied by an increase in cortisol and negative affect which was related to a shift in self-related belief updating towards the positive direction. This self-beneficial belief updating, which was absent after physical stress or control, was associated with a better recovery from stress-induced negative affect. This indicates that enhanced integration of positive self-related feedback can act as a coping strategy to deal with social-evaluative stress.

neuroscience↗

bioRxiv2020

Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the Social Incentive Delay task

Social incentives (rewards or punishments) motivate human learning and behaviour, and alterations in the brain circuits involved in the processing social incentives have been linked with several neuropsychiatric disorders. However, questions still remain about the exact neural substrates implicated in social incentive processing. Here, we conducted four Anisotropic Effect Size Signed Differential Mapping voxel-based meta-analyses of fMRI studies investigating the neural correlates of the anticipation and receipt of social rewards and punishments using the Social Incentive Delay task. We map the regions involved in each of these four processes in the human brain, identify decreases in the BOLD signal during the anticipation of both social reward and punishment avoidance that were missed in individual studies due to a lack of power, and characterise the effect size and direction of changes in the BOLD signal for each brain area. Our results provide a better understanding of the brain circuitry involved in social incentive processing and can inform hypotheses about potentially disrupted brain areas linked with dysfunctional social incentive processing during disease. HighlightsO_LIVoxel-based meta-analysis of the neural underpinnings of social incentive processing C_LIO_LIWe map the brain regions involved in the processing of social incentives in humans C_LIO_LIWe identify new regions missed in individual studies as a result of lack of power C_LIO_LIOur work can inform research on pathological brain processing of social incentives C_LI

neuroscience↗