scholarly journals Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder

2020 ◽  
Vol 10 (12) ◽  
pp. 906
Author(s):  
Max Schneider ◽  
Immanuel G. Elbau ◽  
Teachawidd Nantawisarakul ◽  
Dorothee Pöhlchen ◽  
Tanja Brückl ◽  
...  
Keyword(s):  
Human Subjects ◽  
Pupil Dilation ◽  
Anterior Cingulate ◽  
Dependent Manner ◽  
Targeted Interventions ◽  
Physiological Processes ◽  
Reward Anticipation ◽  
High Prevalence ◽  
Symptom Load ◽  
State Marker

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions.

scholarly journals Reduced arousal during reward anticipation in unmedicated depressed patients

2020 ◽  
Author(s):  
Max Schneider ◽  
Immanuel G. Elbau ◽  
Taechawidd Nantawisarakul ◽  
Dorothee Pöhlchen ◽  
Tanja Brückl ◽  
...  
Keyword(s):  
Pupil Dilation ◽  
Anterior Cingulate ◽  
Group Differences ◽  
Healthy Controls ◽  
Patient Stratification ◽  
Reward Anticipation ◽  
High Prevalence ◽  
Informed Patient ◽  
Depressive States ◽  
Socioeconomic Cost

AbstractDepression is a debilitating disorder with high prevalence and socioeconomic cost, but the central processes that are altered during depressive states remain largely elusive. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. Using pupillometry and concurrent fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls, we observed reduced pupil dilation during reward anticipation in depressed participants with acute symptomatology. We further observed that individual differences in arousal during reward anticipation track the load and impact of depressive symptoms, a correlation that we replicated in a second sample of unmedicated depressed participants. Moreover, these group differences and correlations were mirrored at the neural level. The upregulation and maintenance of arousal during reward anticipation is a translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification.

scholarly journals Systemic, but not local, low-grade endotoxinemia increases plasma sCD163 independently of the cortisol response

2019 ◽  
Vol 8 (2) ◽  
pp. 95-99
Author(s):  
Ermina Bach ◽  
Niels Møller ◽  
Jens Otto L Jørgensen ◽  
Mads Buhl ◽  
Holger Jon Møller
Keyword(s):  
Metabolic Syndrome ◽  
Low Dose ◽  
Human Subjects ◽  
Femoral Vein ◽  
Independent Effect ◽  
Low Grade ◽  
Similar Response ◽  
Dependent Manner ◽  
The Metabolic Syndrome ◽  
And Gender

Aims/hypothesis The macrophage-specific glycoprotein sCD163 has emerged as a biomarker of low-grade inflammation in the metabolic syndrome and related disorders. High sCD163 levels are seen in acute sepsis as a result of direct lipopolysaccharide-mediated shedding of the protein from macrophage surfaces including Kupffer cells. The aim of this study was to investigate if low-grade endotoxinemia in human subjects results in increasing levels of sCD163 in a cortisol-dependent manner. Methods We studied eight male hypopituitary patients and eight age- and gender-matched healthy controls during intravenous low-dose LPS or placebo infusion administered continuously over 360 min. Furthermore, we studied eight healthy volunteers with bilateral femoral vein and artery catheters during a 360-min infusion with saline and low-dose LPS in each leg respectively. Results: Systemic low-grade endotoxinemia resulted in a gradual increase in sCD163 from 1.65 ± 0.51 mg/L (placebo) to 1.92 ± 0.46 mg/L (LPS) at 220 min, P = 0.005 and from 1.66 ± 0.42 mg/L (placebo) to 2.19 ± 0.56 mg/L (LPS) at 340 min, P = 0.006. A very similar response was observed in hypopituitary patients: from 1.59 ± 0.53 mg/L (placebo) to 1.83 ± 0.45 mg/L (LPS) at 220 min, P = 0.021 and from 1.52 ± 0.53 mg/L (placebo) to 2.03 ± 0.44 mg/L (LPS) at 340 min, P < 0.001. As opposed to systemic treatment, continuous femoral artery infusion did not result in increased sCD163. Conclusion: Systemic low-grade endotoxinemia resulted in increased sCD163 to levels seen in the metabolic syndrome in both controls and hypopituitary patients. This suggests a direct and cortisol-independent effect of LPS on the shedding of sCD163. We observed no effect of local endotoxinemia on levels of serum sCD163.

scholarly journals Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 inhibit WRKY75 function in abscisic acid-mediated leaf senescence and seed germination

2021 ◽  
Author(s):  
Haiyan Zhang ◽  
Liping Zhang ◽  
Yunrui Ji ◽  
Yifen Jing ◽  
Lanxin Li ◽  
...  
Keyword(s):  
Abscisic Acid ◽  
Seed Germination ◽  
Leaf Senescence ◽  
Chromatin Immunoprecipitation ◽  
Sigma Factor ◽  
Dependent Manner ◽  
Negative Regulators ◽  
Factor Binding ◽  
Physiological Processes ◽  
Increased Sensitivity

Abstract The plant-specific VQ gene family participates in diverse physiological processes but little information is available on their role in leaf senescence. Here, we show that the VQ motif-containing proteins, Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 are negative regulators of abscisic acid (ABA)-mediated leaf senescence. Loss of SIB1 and SIB2 function resulted in increased sensitivity of ABA-induced leaf senescence. In contrast, overexpression of SIB1 significantly delayed this process. Moreover, biochemical studies revealed that SIBs interact with WRKY75 transcription factor. Loss of WRKY75 function decreased sensitivity to ABA-induced leaf senescence, while overexpression of WRKY75 significantly accelerated this process. Chromatin immunoprecipitation assays revealed that WRKY75 directly binds to the promoters of GOLDEN 2-LIKE1(GLK1) and GLK2, to repress their expression. SIBs repress the transcriptional function of WRKY75 and negatively regulate ABA-induced leaf senescence in a WRKY75-dependent manner. In contrast, WRKY75 positively modulates ABA-mediated leaf senescence in a GLK-dependent manner. In addition, SIBs inhibit WRKY75 function in ABA-mediated seed germination. These results demonstrate that SIBs can form a complex with WRKY75 to regulate ABA-mediated leaf senescence and seed germination.

Syntaxin 12 and COMMD3 are new factors that function with VPS33B in the biogenesis of platelet α-granules

Blood ◽  
2021 ◽  
Author(s):  
Andrea L Ambrosio ◽  
Hallie P Febvre ◽  
Santiago Mauro Di Pietro
Keyword(s):  
Cell Surface ◽  
Dependent Manner ◽  
Bleeding Disorders ◽  
Snare Protein ◽  
Entry And Exit ◽  
Lysosomal Degradation ◽  
Physiological Processes ◽  
Hand Off ◽  
Granule Proteins ◽  
Syntaxin 12

Platelet a-granules regulate hemostasis and myriad other physiological processes but their biogenesis is unclear. Mutations in only three proteins are known to cause a-granule defects and bleeding disorders in humans. Two such proteins, VPS16B and VPS33B, form a complex mediating transport of newly synthesized a-granule proteins through megakaryocyte endosomal compartments. It is unclear how the VPS16B/VPS33B complex accomplishes this function. Here we report VPS16B/VPS33B associates physically with Stx12, a SNARE protein that mediates vesicle fusion at endosomes. Importantly, Stx12 deficient megakaryocytes display reduced a-granule numbers and overall levels of a-granule proteins, thus revealing Stx12 as new component of the a-granule biogenesis machinery. VPS16B/VPS33B also binds CCDC22, a component of the CCC complex working at endosome exit sites. CCDC22 competes with Stx12 for binding to VPS16B/VPS33B suggesting a possible hand-off mechanism. Moreover, the major CCC form expressed in megakaryocytes contains COMMD3, one of ten COMMD proteins. Deficiency of COMMD3/CCDC22 causes reduced a-granule numbers and overall levels of a-granule proteins, establishing the COMMD3/CCC complex as a new factor in a-granule biogenesis. Furthermore, P-Selectin traffics through the cell surface in a COMMD3-dependent manner and depletion of COMMD3 results in lysosomal degradation of P-Selectin and PF4. Stx12 and COMMD3/CCC deficiency cause less severe phenotypes than VPS16B/VPS33B deficiency, suggesting Stx12 and COMMD3/CCC assist but are less important than VPS16B/VPS33B in a-granule biogenesis. Mechanistically, our results suggest VPS16B/VPS33B coordinates the endosomal entry and exit of a-granule proteins by linking the fusogenic machinery with a ubiquitous endosomal retrieval complex that is repurposed in megakaryocytes to make a-granules.

EFFECTS OF ANTERIOR CINGULATE STIMULATION IN CONSCIOUS HUMAN SUBJECTS

1960 ◽  
Vol 23 (4) ◽  
pp. 445-447 ◽  
Author(s):  
W. Lewin ◽  
C. W. M. Whitty
Keyword(s):  
Human Subjects ◽  
Anterior Cingulate

scholarly journals Characterizing Current Attitudes and Practices for Human Subject Safety in Studies Involving Pupil Dilation

2020 ◽  
pp. 155626462096898
Author(s):  
Jacob Szpernal ◽  
Joseph Carroll ◽  
Ryan Spellecy ◽  
Jane A. Bachman Groth
Keyword(s):  
Informed Consent ◽  
Adverse Effects ◽  
Vision Research ◽  
Human Subject ◽  
Human Subjects ◽  
Pupil Dilation ◽  
Institutional Review Boards ◽  
Human Subjects Research ◽  
Attitudes And Practices ◽  
Institutional Review

Standards in pupil dilation practices regarding the safety of human subjects are not present in vision research despite the potential for significant adverse effects. We developed two surveys to examine current practices around pupil dilation among vision researchers and individuals associated with oversight of human subjects research. While both groups note an absence of adverse events associated with pupil dilation, vision researcher practices differed with informed consent use and measures taken to minimize complications. For Institutional Review Boards, general risk assumption associated with dilation was not unanimous and there was a lack of specific guidance available to researchers for minimizing risk. These results uncover the need for standardized practices regarding pupil dilation in human subjects research.

scholarly journals Neurochemical Correlates of Brain Atrophy in Fibromyalgia Syndrome: A Magnetic Resonance Spectroscopy and Cortical Thickness Study

2020 ◽  
Vol 10 (6) ◽  
pp. 395
Author(s):  
Paola Feraco ◽  
Salvatore Nigro ◽  
Luca Passamonti ◽  
Alessandro Grecucci ◽  
Maria Eugenia Caligiuri ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Cortical Thickness ◽  
Inferior Frontal Gyrus ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Dependent Manner ◽  
Cingulate Gyrus ◽  
Concentration Dependent Manner ◽  
The Right

(1) Background: Recently, a series of clinical neuroimaging studies on fibromyalgia (FM) have shown a reduction in cortical volume and abnormally high glutamate (Glu) and glutamate + glutamine (Glx) levels in regions associated with pain modulation. However, it remains unclear whether the volumetric decreases and increased Glu levels in FM are related each other. We hypothesized that higher Glu levels are related to decreases in cortical thickness (CT) and volume in FM patients. (2) Methods: Twelve females with FM and 12 matched healthy controls participated in a session of combined 3.0 Tesla structural magnetic resonance imaging (MRI) and single-voxel MR spectroscopy focused on the thalami and ventrolateral prefrontal cortices (VLPFC). The thickness of the cortical and subcortical gray matter structures and the Glu/Cr and Glx/Cr ratios were estimated. Statistics included an independent t-test and Spearman’s test. (3) Results: The Glu/Cr ratio of the left VLPFC was negatively related to the CT of the left inferior frontal gyrus (pars opercularis (p = 0.01; r = −0.75) and triangularis (p = 0.01; r = −0.70)). Moreover, the Glx/Cr ratio of the left VLPFC was negatively related to the CT of the left middle anterior cingulate gyrus (p = 0.003; r = −0.81). Significantly lower CTs in FM were detected in subparts of the cingulate gyrus on both sides and in the right inferior occipital gyrus (p < 0.001). (4) Conclusions: Our findings are in line with previous observations that high glutamate levels can be related, in a concentration-dependent manner, to the morphological atrophy described in FM patients.

scholarly journals Parallel Information Processing in Motor Systems: Intracerebral Recordings of Readiness Potential and CNV in Human Subjects

2000 ◽  
Vol 7 (1-2) ◽  
pp. 65-72 ◽  
Author(s):  
Ivan Rektor
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Human Subjects ◽  
Anterior Cingulate ◽  
Readiness Potential ◽  
Task Context ◽  
Subcortical Structures ◽  
Depth Electrodes ◽  
Simultaneous Activation

We performed intracerebral recordings of Readiness Potential (RP) and Contingent Negative Variation (CNV) with simple repetitive distal limb movement in candidates for epilepsy surgery. In 26 patients (in Paris), depth electrodes were located in various cortical structures; in eight patients (in Brno), in the basal ganglia and the cortex. RPs were displayed in the conteral primary motor cortex, conteral somato-sensory cortex, and bilaterally in the SMA and the caudal part of the anterior cingulate cortices. CNVs were recorded in the same cortical regiom as the RP, as well as in the ipsilateral primary motor cortex, and bilaterally in the premotor fronto-lateral, parietal superior, and middle temporal regions. In the basal ganglia, the RP was recorded in the putamen in six of seven patients, and in the head of the caudate nucleus and the pallidum in the only patient with electrodes in these recording sites. We suggest that our results are consistent with a long-lasting, simultaneous activation of cortical and subcortical structures, before and during self-paced and stimulus-triggered movements. The particular regiom that are simultaneously active may be determined by the task context.

scholarly journals Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C57BL/6J mice

2015 ◽  
Vol 4 ◽  
Author(s):  
Yoshie Fujii ◽  
Noriko Osaki ◽  
Tadashi Hase ◽  
Akira Shimotoyodome
Keyword(s):  
Insulin Secretion ◽  
Human Subjects ◽  
Coffee Consumption ◽  
Epidemiological Studies ◽  
Diabetes Risk ◽  
Dependent Manner ◽  
Diabetes In Animals ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dose Dependent

AbstractThe widespread prevalence of diabetes, caused by impaired insulin secretion and insulin resistance, is now a worldwide health problem. Glucagon-like peptide 1 (GLP-1) is a major intestinal hormone that stimulates glucose-induced insulin secretion from β cells. Prolonged activation of the GLP-1 signal has been shown to attenuate diabetes in animals and human subjects. Therefore, GLP-1 secretagogues are attractive targets for the treatment of diabetes. Recent epidemiological studies have reported that an increase in daily coffee consumption lowers diabetes risk. The present study examined the hypothesis that the reduction in diabetes risk associated with coffee consumption may be mediated by the stimulation of GLP-1 release by coffee polyphenol extract (CPE). GLP-1 secretion by human enteroendocrine NCI-H716 cells was augmented in a dose-dependent manner by the addition of CPE, and was compatible with the increase in observed active GLP-1(7–36) amide levels in the portal blood after administration with CPE alone in mice. CPE increased intracellular cyclic AMP (cAMP) levels in a dose-dependent manner, but this was not mediated by G protein-coupled receptor 119 (GPR119). The oral administration of CPE increased diet (starch and glyceryl trioleate)-induced active GLP-1 secretion and decreased glucose-dependent insulinotropic polypeptide release. Although CPE administration did not affect diet-induced insulin secretion, it decreased postprandial hyperglycaemia, which indicates that higher GLP-1 levels after the ingestion of CPE may improve insulin sensitivity. We conclude that dietary coffee polyphenols augment gut-derived active GLP-1 secretion via the cAMP-dependent pathway, which may contribute to the reduced risk of type 2 diabetes associated with daily coffee consumption.

scholarly journals Orphan receptor GPR158 controls stress-induced depression

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Laurie P Sutton ◽  
Cesare Orlandi ◽  
Chenghui Song ◽  
Won Chan Oh ◽  
Brian S Muntean ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Orphan Receptor ◽  
Dependent Manner ◽  
Depression And Anxiety ◽  
Major Depressive ◽  
Protein Levels ◽  
Pharmacological Target ◽  
Decisive Action

Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the PFC in a glucocorticoid-dependent manner. Viral overexpression of GPR158 in the PFC induced depressive-like behaviors. In contrast GPR158 ablation, led to a prominent antidepressant-like phenotype and stress resiliency. We found that GPR158 exerts its effects via modulating synaptic strength altering AMPA receptor activity. Taken together, our findings identify a new player in mood regulation and introduce a pharmacological target for managing depression.

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