Quercetin alleviates chronic unpredictable mild stress‐induced depression‐like behavior by inhibiting NMDAR1 with α2δ‐1 in rats

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(4)

Опубликована: Апрель 1, 2024

Abstract Background Depression is a serious mental disorder and the most prevalent cause of disability suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to significant acceleration depression development. Quercetin (Que) flavonoid compound with wide range pharmacological effects. Recent studies have shown that quercetin improve CUMS‐induced depression‐like behavior, but mechanism its improvement still unclear. α2δ‐1 regulatory subunit voltage‐gated calcium channel, which interact N‐methyl‐D‐aspartate receptor (NMDAR) form complex. Objective In this study, we found Que could inhibit increase NMDAR expression in rat hypothalamus induced by CUMS. pain, chronic hypertension other interacts complex, subsequently affects level NMDAR. Consequently, present study aimed investigate antidepressant effect vivo vitro explore action terms interaction between Methods Rats were randomly exposed two stressors every day for 4 weeks establish CUMS model, then sucrose preference test (SPT), forced swimming (FST), tail suspension (TST), open field (OFT) performed detect behavior rats, so as evaluate whether model was successfully established on rats. Experimental techniques such serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, co‐immunoprecipitation, well experiments, used mechanisms exerts Results Behavioral ELISA results showed produce reduction excitability hypothalamic–pituitary–adrenal (HPA) axis rats improvements their depressive behavior. co‐immunoprecipitation experiments produced decrease NMDAR1 levels interfered binding. addition, neural regulation PC12 cells knocked out gene further verified. Cellular demonstrated led reversal up‐regulation corticosterone‐injured cells, while had no effects knockout. Conclusions has good significantly caused It inhibiting α2δ‐1, interfering NMDAR, reducing HPA axis.

Язык: Английский

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Polygenic risk for depression and resting-state functional connectivity of subgenual anterior cingulate cortex in young adults

Journal of Psychiatry and Neuroscience, Год журнала: 2025, Номер 50(1), С. E31 - E44

Опубликована: Янв. 14, 2025

Genetic variants may confer risk for depression by modulating brain structure and function; evidence has underscored the key role of subgenual anterior cingulate cortex (sgACC) in depression. We sought to examine how resting-state functional connectivity (rsFC) sgACC was associated with polygenic a subclinical population. Following published protocols, we computed seed-based whole-brain rsFC calculated scores (PRS) using data from healthy young adults Human Connectome Project. performed regression against PRS severity symptoms single model all participants sex, controlling age, race or ethnicity, alcohol use severity, household income. evaluated results at corrected threshold. included 717 adults. found lower between default mode network frontal regions association sgACC-cerebellar severity. also noted differences sex correlates In an additional set analyses, observed significant correlation somatic complaints, as well altered sgACC-somatosensory cortical complaints. The current findings should be considered specific not generalize patients depressive disorders. Our highlight pivotal distinct sgACC-based networks genetic predisposition manifestation among Distinguishing markers have implications developing early effective treatments people

Язык: Английский

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Functional Connectivity Alterations Associated with COVID-19-Related Sleep Problems: A Longitudinal Resting-State fMRI Study

Nature and Science of Sleep, Год журнала: 2025, Номер Volume 17, С. 97 - 113

Опубликована: Янв. 1, 2025

COVID-19 has led to reports of fatigue and sleep problems. Brain function changes underlying problems (SP) post-COVID-19 are unclear. This study investigated SP-related brain functional connectivity (FC) alterations. Fifty-five survivors with SP (COVID_SP) 33 without (COVID_NSP), matched for demographics, completed PSQI underwent rs-fMRI at baseline 2-month follow-up. Correlations between FC clinical data were analyzed by Pearson correlation analysis Gaussian random field (GRF) correction. The repeated-measures variance (R-M ANOVA) was explore the interaction time. At baseline, COVID_SP exhibited elevated FC: right precentral gyrus (PrG) left lateral occipital cortex (LOcC)/right PrG, inferior parietal lobule (IPL) superior frontal (SFG), hippocampus (IFG). Higher SFG correlated scores. follow-up, decreased implicated in emotion regulation, executive function, memory; increased semantics, attention, auditory-visual processing. these regions scores PSQI, GAD, PHQ. Repeated-Measures Analysis Variance revealed a significant time effect various scales. Moreover, PrG as well that IPL also discovered effect. provides insight into associated after COVID-19. These may partially explain development SP, they changed over

Язык: Английский

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Structural and functional alterations in hypothalamic subregions in male patients with alcohol use disorder

Drug and Alcohol Dependence, Год журнала: 2025, Номер 268, С. 112554 - 112554

Опубликована: Янв. 16, 2025

Язык: Английский

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Connectomics modeling of regional networks of white-matter fractional anisotropy to predict the severity of young adult drinking

Quantitative Imaging in Medicine and Surgery, Год журнала: 2025, Номер 15(3), С. 2405 - 2419

Опубликована: Март 1, 2025

Alcohol use impacts brain structure, including white matter integrity, which can be quantified by fractional anisotropy (FA) in diffusion tensor imaging (DTI). This study explored the relationship between severity of alcohol consumption and FA changes, its sex differences, young adults, using data from Human Connectome Project. We analyzed DTI 949 participants (491 females) used principal component analysis (PCA) 15 drinking metrics to quantify severity. Connectome-based predictive modeling (CPM) was employed predict network values a matrix 116×116 regions. Mediation analyses were conducted explore interrelationships among networks identified CPM, severity, rule-breaking behavior. Significant correlations found values. Both men women showed significant negative connectivity (men: r=0.15, P=0.001; women: r=0.30, P<0.001). Sex differences observed regions contributing predictions. revealed inter-relationships features, The connectomics consumption, incorporating pathways, identify differences. approach provides new clues biological basis abuse evaluates how these interact broader for understanding misuse comorbidities.

Язык: Английский

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Modular network analysis of abnormal functional connectivity and disrupted brain topology caused by sleep deprivation and its association with cognitive function

Sleep Medicine, Год журнала: 2025, Номер unknown, С. 106514 - 106514

Опубликована: Апрель 1, 2025

Язык: Английский

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Altered Hypothalamic Functional Connectivity after Partial Sleep Deprivation in Young and Elderly Adults

Behavioural Brain Research, Год журнала: 2025, Номер unknown, С. 115587 - 115587

Опубликована: Апрель 1, 2025

Язык: Английский

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Ebastine in combination with low-dose antidepressants for refractory irritable bowel syndrome: A randomized controlled trial

Technology and Health Care, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

Background Drug treatment of refractory irritable bowel syndrome (IBS) is not satisfactory at present. This study investigated the clinical effects ebastine combined with low-dose antidepressants on IBS. Methods A total 105 patients IBS were randomly assigned to two different groups after signing informed consent. And they didn't know about group in. They administered (Group A) or flupentixol and melitracen B) for 4 weeks. efficacy was evaluated using scales before treatment. In addition, serum D-lactate (D-LAC) human intestinal fatty acid binding protein (I-FABP) level measured assess permeability. Results Significant improvements observed in Quality Life (IBS-QOL) score, Symptom Severity Scale (IBS-SSS) sleep quality score. Patients Group showed no anxiety (44.83 ± 9.62 vs. 43.92 10.43, P = 0.415) depression (39.08 9.34 38.75 9.35, 0.674) compared baseline level, while those B improved significantly (52.12 8.19 39.28 9.88) (47.64 9.53 38.24 9.41) status. After treatment, levels D-LAC I-FABP lower than A. Conclusion Refractory certain psychological abnormalities. Ebastine exhibited more obvious benefits QOL, quality, SSS, significant status permeability patients.

Язык: Английский

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Polygenic risk for depression and resting state functional connectivity of subgenual anterior cingulate cortex in young adults

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 21, 2024

Abstract Genetic variants may confer risks for depression by modulating brain structure and function. Prior evidence has underscored a key role of the subgenual anterior cingulate cortex (sgACC) in depression. Here, we built on literature examined how resting state functional connectivity (rsFC) sgACC was associated with polygenic We followed published routines computed seed-based whole-brain rsFC risk scores (PRS) 717 young adults curated from Human Connectome Project. performed regression against PRS severity symptoms single model all subjects men women alone, controlling age, sex (for all), race, alcohol use, household income, evaluated results at corrected threshold. found lower default mode network frontal regions association sgACC-cerebellar severity. also noted differences correlates In an additional set analyses, observed significant correlation between somatic complaints score altered sgACC-somatosensory cortical link complaints. Our findings collectively highlighted pivotal distinct sgACC-based networks genetic predisposition to clinical manifestation Distinguishing markers have implications developing early effective treatments individuals

Язык: Английский

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Functional Networks of Reward and Punishment Processing and Their Molecular Profiles Predicting the Severity of Young Adult Drinking

Brain Sciences, Год журнала: 2024, Номер 14(6), С. 610 - 610

Опубликована: Июнь 18, 2024

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to the molecular profiles of connectivity features predicting alcohol use severity in young adults. We curated Human Connectome Project data employed connectome-based predictive modeling (CPM) examine how functional (FC) during wins losses are severity, quantified by Semi-Structured Assessment for Genetics Alcoholism, 981 combined CPM findings JuSpace toolbox characterize severity. The connectomics appeared specific, comprising less than 0.12% all features, including medial frontal, motor/sensory, cerebellum/brainstem networks processing fronto-parietal, motor/sensory Spatial correlation analyses showed that these were predominantly serotonergic GABAa signaling. To conclude, a distinct pattern predicted adult drinkers. These “neural fingerprints” elucidate impacts brain provide evidence new targets future intervention.

Язык: Английский

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