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Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.
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Resistencia a los Herbicidas , Herbicidas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento/métodos , Plantas Modificadas Genéticamente/genética , MutaciónRESUMEN
The purpose of the present study was to estimate the factors linked to the prognosis of children with provisional tic disorder (PTD). We conducted a prospective cohort study enrolled children with PTD who were subsequently followed-up at three-month intervals for 1 year post-enrolment. A total of 259 PTD patients were included in the final analysis. At the end of the follow-up period, 77 (30%) of the patients had achieved clinical remission. Result of the LASSO logistic regression analysis revealed that a disease duration >3 months (OR=4.20, 95% CI 1.20-14.73), moderate/severe tic severity (OR=5.57, 95% CI 2.26-13.76), and comorbid behavioral problems (OR=2.78, 95% CI 1.15-6.69) were significant factors linked to remission in the PTD patients. The path analysis model showed that comorbid behavioral problems and recurrence partially mediated the association between tic severity and remission, with a mediating effect of 37%. Conclusions: We have identified several significant factors linked to prognosis in children with PTD, including comorbid behavioral problems and recurrence, which were found to be important mediators. These findings provide new insights for the clinical management of patients with PTD.
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Trastornos de Tic , Humanos , Trastornos de Tic/epidemiología , Trastornos de Tic/diagnóstico , Masculino , Femenino , Estudios Prospectivos , Niño , Pronóstico , Preescolar , Recurrencia , Estudios de Seguimiento , Índice de Severidad de la Enfermedad , Adolescente , Factores de Riesgo , Comorbilidad , Modelos LogísticosRESUMEN
Depression is considered a crucial psychiatric disease correlated with neuronal-dysfunctions induced by stress-stimuli. This study aimed to investigate effect of Fluoxetine (FL) on chronic unpredictable mild stress (CUMS) and explore the associated mechanisms. CUMS rat model was established by treating with lots of stresses. CUMS rats were administered FL, SB216763 (SB), Wortmannin (WT) alone or in combination. CUMS rats were administered 1 % sugar water to conduct sugar water consumption experiment. Acet-Tub, Tyr-Tub, tau46, p-tau-Ser199/202, p-tau-Ser396, p-tau-Ser231, expression was examined using immunohistochemical assay and western blotassay. Interaction between tau and tubulin was evaluated with immunoprecipitation assay. Double immunohistochemical assay was used to identify interaction between Nestin and Tau. The results indicated that FL treatment only increased sugar consumption of CUMS rats (P < 0.05), but also strengthened effects of SB and WT. FL significantly treatment decreased tau phosphorylation (p-tau) in hippocampal tissues of rats compared to those of rats in CUMS group (P < 0.05). FL treatment markedly decreased Acet-Tub and increased Tyr-Tub expression in hippocampal tissues of rats compared to those of rats in CUMS group (P < 0.05). The effects of FL treatment on p-tau down-regulation and tubulin modulation in hippocampal tissues were independent from PI3K and GSK-3 signaling pathways. FL treatment could also enhance proliferation and total tau of newborn neurons of CUMS rats. FL treatment strengthened interaction between tau and botulin in hippocampal tissues of CUMS rats. In conclusion, Fluoxetin suppressed phosphorylation of tau and modulated the interaction between tau and tubulin in hippocampus of adult CUMS rats.
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Hipocampo , Ratas Sprague-Dawley , Estrés Psicológico , Tubulina (Proteína) , Proteínas tau , Animales , Proteínas tau/metabolismo , Tubulina (Proteína)/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Masculino , Estrés Psicológico/metabolismo , Estrés Psicológico/tratamiento farmacológico , RatasRESUMEN
Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.
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Ansiedad , Hipocampo , Proteína con Dominio Pirina 3 de la Familia NLR , Periodo Posparto , Prolactina , Receptores de Prolactina , Animales , Femenino , Prolactina/sangre , Prolactina/metabolismo , Hipocampo/metabolismo , Embarazo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ansiedad/metabolismo , Receptores de Prolactina/metabolismo , Ratones , Periodo Posparto/metabolismo , Condicionamiento Físico Animal/fisiología , Depresión Posparto/metabolismo , Depresión Posparto/prevención & control , Depresión/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Carrera/fisiología , Carrera/psicologíaRESUMEN
Objectives: Sex-specific differences in internet gaming disorder (IGD) neurophysiology remain underexplored. Here we investigated sex-related variability in regional homogeneity (ReHo) and functional connectivity (FC) in IGD and their correlations with sleep quality. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 52 subjects with IGD and 50 healthy controls (HCs). Two-way ANOVA was used to examine sex and diagnosis interactions in ReHo and FC, followed by post-hoc analyses to explore FC biomarkers for different sexes. Results: In ReHo analysis, the four groups showed significant sex and diagnosis interactions in the right middle frontal gyrus (rMFG). FC analysis with rMFG as the seed region revealed a significant sex and diagnosis interaction effect in FC of the rMFG with the bilateral postcentral gyrus (PoCG). In male IGD group, FC between the rMFG and the bilateral PoCG correlates strongly with daytime dysfunction score and the Pittsburgh sleep quality inventory (PSQI) total score. Conclusion: These findings emphasize the importance of considering sexual dimorphism in the neurobiology of IGD, which might influence subsequent treatment strategies.
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Previous research has shown a decrease in serum testosterone levels in male patients with depression. In recent years, the results of testosterone replacement therapy (TRT) to improve depression have been mixed. Using the classic CUMS model, we induced depressive-like behaviors in rats and observed a decrease in their serum testosterone levels along with an increase in androgen receptor expression in the hippocampus. We then performed castration and sham surgery on male rats and found that testosterone deprivation led to the manifestation of depressive-like behavior that could be ameliorated by TRT. Through a repeated measures experiment consisting of five blocks over a period of 25 days, we discovered that the reduction in depressive-like behavior in testosterone-deprived rats began 22 days after drug administration (0.5 and 0.25â¯mg/rat). Furthermore, rats in 0.5mgT group showed the most significant improvements. Subsequently, this dose was used in CUMS rats and reduced the occurrence of depressive-like behaviors. Our study has demonstrated the complex interplay between depression and testosterone, as well as the intricate dose-response relationship between TRT and reduction in depression. Our research supports the use of TRT to alleviate depression, but dosage and duration of treatment are critical factors in determining efficacy.
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Conducta Animal , Depresión , Orquiectomía , Testosterona , Animales , Masculino , Testosterona/farmacología , Testosterona/administración & dosificación , Testosterona/metabolismo , Ratas , Depresión/tratamiento farmacológico , Depresión/metabolismo , Conducta Animal/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Relación Dosis-Respuesta a Droga , Terapia de Reemplazo de Hormonas/métodos , Receptores Androgénicos/metabolismo , Receptores Androgénicos/efectos de los fármacosRESUMEN
Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.
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Arterial spin labeling (ASL) can be used to detect differences in perfusion for multiple brain regions thought to be important in major depressive disorder (MDD). However, the potential of cerebral blood flow (CBF) to predict MDD and its correlations between the blood lipid levels and immune markers, which are closely related to MDD and brain function change, remain unclear. The 451 individuals - 298 with MDD and 133 healthy controls who underwent MRI at a single time point with arterial spin labelling and a high resolution T1-weighted structural scan. A proportion of MDD also provided blood samples for analysis of lipid and immune markers. We performed CBF case-control comparisons, random forest model construction, and exploratory correlation analyses. Moreover, we investigated the relationship between gray matter volume (GMV), blood lipids, and the immune system within the same sample to assess the differences in CBF and GMV. We found that the left inferior parietal but supramarginal and angular gyrus were significantly different between the MDD patients and HCs (voxel-wise P < 0.001, cluster-wise FWE correction). And bilateral inferior temporal (ITG), right middle temporal gyrus and left precentral gyrus CBF predict MDD (the area under the receiver operating characteristic curve of the random forest model is 0.717) and that CBF is a more sensitive predictor of MDD than GMV. The left ITG showed a positive correlation trend with immunoglobulin G (r = 0.260) and CD4 counts (r = 0.283). The right ITG showed a correlation trend with Total Cholesterol (r = -0.249) and tumour necrosis factor-alpha (r = -0.295). Immunity and lipids were closely related to CBF change, with the immunity relationship potentially playing a greater role. The interactions between CBF, plasma lipids and immune index could therefore represent an MDD pathophysiological mechanism. The current findings provide evidence for targeted regulation of CBF or immune properties in MDD.
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Trastorno Depresivo Mayor , Sustancia Gris , Humanos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Depresión , Encéfalo/patología , Imagen por Resonancia Magnética , Circulación Cerebrovascular/fisiología , Marcadores de Spin , Biomarcadores , LípidosRESUMEN
Objectives: Major Depressive Disorder (MDD) is significantly influenced by childhood trauma (CT), affecting brain anatomy and functionality. Despite the unique disease trajectory in MDD patients with CT, the underlying neurobiological mechanisms remain unclear. Our objective is to investigate CT's impact on the white matter structure of the brain in patients with MDD. Methods: This research employed tract-based spatial statistics (TBSS) to detect variations between groups in Fractional Anisotropy (FA) throughout the whole brain in 71 medication-free MDD patients and 97 HCs. Participants filled out the Childhood Trauma Questionnaire (CTQ) and assessments for depression and anxiety symptoms. The relationship between FA and CTQ scores was explored with partial correlation analysis, adjusting for factors such as age, gender, educational background, and length of illness. Results: Compared to HCs, the MDD group showed decreased FA values in the right posterior limb of the internal capsule (PLIC), the inferior fronto-occipital fasciculus (IFOF), and bilateral superior longitudinal fasciculus (SLF). Simple effects analysis revealed that compared to HC-CT, the MDD-CT group demonstrated decreased FA values in right PLIC, IFOF, and bilateral SLF. The MDD-nCT group showed decreased FA values in right PLIC and IFOF compared to HC-nCT. The total scores and subscale scores of CTQ were negatively correlated with the FA in the right SLF. Conclusion: The right SLF may potentially be influenced by CT during the brain development of individuals with MDD. These results enhance our knowledge of the role of the SLF in the pathophysiology of MDD and the neurobiological mechanisms by which CT influences MDD.
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The anterior cingulate cortex (ACC) is a heterogeneous region of the brain's limbic system that regulates cognitive and emotional processing, and is frequently implicated in schizophrenia. This study aims to characterize resting-state functional connectivity (rsFC) profiles of three subregions of ACC in patients with first-episode schizophrenia and healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from 60 first-episode schizophrenia (FES) patients and 60 healthy controls (HC), and the subgenual ACC (sgACC), pregenual ACC (pgACC), and dorsal ACC (dACC) were selected as seed regions from the newest automated anatomical labeling atlas 3 (AAL3). Seed-based rsFC maps for each ACC subregion were generated and compared between the two groups. The results revealed that compared to the HC group, the FES group showed higher rsFC between the pgACC and bilateral lateral orbitofrontal cortex (lOFC), and lower rsFC between the dACC and right posterior OFC (pOFC), the medial prefrontal gyrus (MPFC), and the precuneus cortex (PCu). These findings point to a selective functional dysconnectivity of pgACC and dACC in schizophrenia and provide more accurate information about the functional role of the ACC in this disorder.
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Mapeo Encefálico , Giro del Cíngulo , Imagen por Resonancia Magnética , Vías Nerviosas , Descanso , Esquizofrenia , Humanos , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Esquizofrenia/fisiopatología , Esquizofrenia/diagnóstico por imagen , Masculino , Imagen por Resonancia Magnética/métodos , Femenino , Adulto Joven , Adulto , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Mapeo Encefálico/métodos , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagenRESUMEN
BACKGROUND: Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes a heavy burden on individuals, families and society. Previous studies on MDD predominantly focused on neurons and employed bulk homogenates of brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development and MDD at the single-cell resolution level. METHODS: Here, we present the use of a guided regularized random forest (GRRF) algorithm to explore single-nucleus RNA sequencing profiles (GSE144136) of the OL at four developmental stages, which contains dorsolateral prefrontal cortex of 17 healthy controls (HC) and 17 MDD cases, generated by Nagy C et al. We prioritized and ordered differentially expressed genes (DEGs) based on Nagy et al., which could predominantly discriminate cells in the four developmental stages and two adjacent developmental stages of the OL. We further screened top-ranked genes that distinguished between HC and MDD in four developmental stages. Moreover, we estimated the performance of the GRRF model via the area under the curve value. Additionally, we validated the pivotal candidate gene Malat1 in animal models. RESULTS: We found that, among the four developmental stages, the onset development of OL (OPC2) possesses the best predictive power for distinguishing HC and MDD, and long noncoding RNA MALAT1 has top-ranked importance value in candidate genes of four developmental stages. In addition, results of fluorescence in situ hybridization assay showed that Malat1 plays a critical role in the occurrence of depression. CONCLUSIONS: Our work elucidates the mechanism of MDD from the perspective of OL development at the single-cell resolution level and provides novel insight into the occurrence of depression.
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Trastorno Depresivo Mayor , ARN Largo no Codificante , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , Linaje de la Célula/genética , Hibridación Fluorescente in Situ , ARN Largo no Codificante/metabolismo , Corteza Prefrontal/metabolismo , Perfilación de la Expresión Génica , Expresión GénicaRESUMEN
BACKGROUND: Many metabolomics studies of depression have been performed, but these have been limited by their scale. A comprehensive in silico analysis of global metabolite levels in large populations could provide robust insights into the pathological mechanisms underlying depression and candidate clinical biomarkers. METHODS: Depression-associated metabolomics was studied in 2 datasets from the UK Biobank database: participants with lifetime depression (N = 123,459) and participants with current depression (N = 94,921). The Whitehall II cohort (N = 4744) was used for external validation. CatBoost machine learning was used for modeling, and Shapley additive explanations were used to interpret the model. Fivefold cross-validation was used to validate model performance, training the model on 3 of the 5 sets with the remaining 2 sets for validation and testing, respectively. Diagnostic performance was assessed using the area under the receiver operating characteristic curve. RESULTS: In the lifetime depression and current depression datasets and sex-specific analyses, 24 significantly associated metabolic biomarkers were identified, 12 of which overlapped in the 2 datasets. The addition of metabolic features slightly improved the performance of a diagnostic model using traditional (nonmetabolomics) risk factors alone (lifetime depression: area under the curve 0.655 vs. 0.658 with metabolomics; current depression: area under the curve 0.711 vs. 0.716 with metabolomics). CONCLUSIONS: The machine learning model identified 24 metabolic biomarkers associated with depression. If validated, metabolic biomarkers may have future clinical applications as supplementary information to guide early and population-based depression detection.
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Biomarcadores , Aprendizaje Automático , Metabolómica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/metabolismo , Anciano , Macrodatos , Depresión/metabolismo , Depresión/diagnóstico , Adulto , Trastorno Depresivo/metabolismo , Trastorno Depresivo/diagnósticoRESUMEN
The neuroinflammatory state may contribute to the pathogenesis of many mental disorders including schizophrenia. Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for activation of proteins involved in mitochondria quality control, such as Sirtuin3 (SIRT3). Our previous study has found that NAD+ supplement could rescue early life stress (ELS)-induced neuroinflammation and down-regulation of SIRT3 in adult offspring. However, it is unclear whether SIRT3 is the key to the neuroprotective effects of NAD+ supplement in this animal model of schizophrenia. The present study used 24 h maternal separation (MS) as ELS to Wistar rat pups on the postnatal day (PND) 9. Schizophrenia-like behaviors and memory impairments were detected by behavioral tests. Microglial activation, pro-inflammatory cytokine expression, and NAD+/SIRT3 expression were detected in the prefrontal cortex and hippocampus. Meanwhile, NAM (a precursor of NAD+), and the SIRT3 activator Honokiol (HNK), and the SIRT3 inhibitor 3-TYP were used as an intervention in vivo. Our results showed that ELS could induce schizophrenia-like behaviors and M1 microglial activation, NAD+ decline, lower expression of SIRT3, and increased acetylated superoxide dismutase 2 expression at the adult stage. NAD+ supplement or HNK administration could block this process and normalize the behavioral alterations of the MS animals. 3-TYP administration in the control group and the NAM-treated MS rats caused M1 microglial activation and cognitive deficits. Our results demonstrated that SIRT3 mediated the stabilizing effect of NAD+ on normalizing M1 microglial activation and behavioral phenotypes in MS rats.
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Esquizofrenia , Sirtuina 3 , Animales , Humanos , Ratas , Cognición , Privación Materna , NAD , Enfermedades Neuroinflamatorias , Ratas Wistar , Esquizofrenia/complicaciones , Sirtuina 3/metabolismoRESUMEN
Postmenopausal women face a higher risk of depression due to a combination of social and physiological factors. As a beverage rich in a variety of bioactive substances, green tea has significant effects on metabolism, inflammation and endocrine, and may reduce the risk of depression, but few studies have looked at the effects of green tea on postmenopausal women. Therefore, we designed this study to investigate the effects of long-term green tea consumption on inflammation, endocrine and depression levels in postmenopausal women. We investigated a tea-producing village and eventually included 386 postmenopausal women, both in the tea drinking and control groups. The results showed that there were significant differences in the degree of insomnia, degree of depression, BMI, SII and estradiol between the two groups. And, green tea consumption may reduce the risk of depression through the mediating pathway of sleep, SII and estradiol. In summary, long-term green tea consumption can reduce the risk of depression in postmenopausal women by reducing inflammation and increasing estradiol. This kind of living habit deserves further promotion.
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Estradiol , Té , Humanos , Femenino , Posmenopausia/fisiología , Depresión/prevención & control , InflamaciónRESUMEN
Early adverse life events (EALs) increase susceptibility to depression and impair cognitive performance, but the physiological mechanisms are still unclear. The target of this article is to clarify the impact of adverse childhood experiences on emotional and cognitive performance from the perspective of the heart-brain axis. We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to test cognitive function and the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Heart rate variability (HRV) and electroencephalograms (EEG) were acquired at rest. We observed that subjects with depression had experienced more traumatic events during their childhood. Furthermore, they exhibited lower heart rate variability and higher power in the delta, theta, and alpha frequency bands. Moreover, heart rate variability partially mediated the association between childhood trauma exposure and depressive symptoms. Our findings suggested that adverse life events in childhood could influence the development of depression in adulthood, which might be linked to cardiac autonomic dysfunction and altered brain function.
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BACKGROUND: The accumulation and aggregation of α-synuclein (α-Syn) are characteristic of Parkinson's disease (PD). Epidemiological evidence indicates that hyperlipidemia is associated with an increased risk of PD. The levels of 27-hydroxycholesterol (27-OHC), a cholesterol oxidation derivative, are increased in the brain and cerebrospinal fluid of patients with PD. However, whether 27-OHC plays a role in α-Syn aggregation and propagation remains elusive. OBJECTIVE: The aim of this study was to determine whether 27-OHC regulates α-Syn aggregation and propagation. METHODS: Purified recombinant α-Syn, neuronal cultures, and α-Syn fibril-injected mouse model of PD were treated with 27-OHC. In addition, CYP27A1 knockout mice were used to investigate the effect of lowering 27-OHC on α-Syn pathology in vivo. RESULTS: 27-OHC accelerates the aggregation of α-Syn and enhances the seeding activity of α-Syn fibrils. Furthermore, the 27-OHC-modified α-Syn fibrils localize to the mitochondria and induce mitochondrial dysfunction and neurotoxicity. Injection of 27-OHC-modified α-Syn fibrils induces enhanced spread of α-Syn pathology and dopaminergic neurodegeneration compared with pure α-Syn fibrils. Similarly, subcutaneous administration of 27-OHC facilitates the seeding of α-Syn pathology. Genetic deletion of cytochrome P450 27A1 (CYP27A1), the enzyme that converts cholesterol to 27-OHC, ameliorates the spread of pathologic α-Syn, degeneration of the nigrostriatal dopaminergic pathway, and motor impairments. These results indicate that the cholesterol metabolite 27-OHC plays an important role in the pathogenesis of PD. CONCLUSIONS: 27-OHC promotes the aggregation and spread of α-Syn. Strategies aimed at inhibiting the CYP27A1-27-OHC axis may hold promise as a disease-modifying therapy to halt the progression of α-Syn pathology in PD. © 2023 International Parkinson and Movement Disorder Society.
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Enfermedad de Parkinson , Humanos , Ratones , Animales , Enfermedad de Parkinson/genética , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Hidroxicolesteroles/farmacología , ColesterolRESUMEN
Schizophrenia and depression are psychiatric disorders with overlapping clinical and biological features. This study aimed to identify common and distinct neuropathological mechanisms in schizophrenia and depression patients using resting-state functional magnetic resonance imaging (fMRI). The study included 28 patients with depression (DEP), 29 patients with schizophrenia (SCH), and 30 healthy control subjects (HC). Intrinsic connectivity contrast (ICC) was used to identify functional connectivity (FC) changes at the whole-brain level, and significant ICC differences were found in the bilateral orbitofrontal cortex (OFC) across all three groups. Further seed-based FC analysis indicated that compared to the DEP and HC groups, the FC between bilateral OFC and medial prefrontal cortex (MPFC), right anterior insula, and right middle frontal gyrus were significantly lower in the SCH group. Additionally, the FC between right OFC and left thalamus was decreased in both patient groups compared to the HC group. Correlation analysis showed that the FC between OFC and MPFC was positively correlated with cognitive function in the SCH group. These findings suggest that OFC connectivity plays a critical role in the pathophysiology of schizophrenia and depression and may provide new insights into the potential neural mechanisms underlying these two disorders.
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OBJECTIVE: Previous studies have revealed the frontoparietal network (FPN) plays a key role in the imaging pathophysiology of bipolar disorder (BD). However, network homogeneity (NH) in the FPN among bipolar mania (BipM), remitted bipolar disorder (rBD), and healthy controls (HCs) remains unknown. The present study aimed to explore whether NH within the FPN can be used as an imaging biomarker to differentiate BipM from rBD and to predict treatment efficacy for patients with BipM. METHODS: Sixty-six patients with BD (38 BipM and 28 rBD) and 60 HCs participated in resting-state functional magnetic resonance imaging and neuropsychological tests. Independent component analysis and NH analysis were applied to analyze the imaging data. RESULTS: Relative to HCs, BipM patients displayed increased NH in the left middle frontal gyrus (MFG), and rBD patients displayed increased NH in the right inferior parietal lobule (IPL). Compared to rBD patients, BipM patients displayed reduced NH in the right IPL. Furthermore, support vector machine results exhibited that NH values in the right IPL could distinguish BipM patients from rBD patients with 69.70 %, 57.89 %, and 91.67 % for accuracy, sensitivity, and specificity, respectively, and support vector regression results exhibited a significant association between predicted and actual symptomatic improvement based on the reduction ratio of the Young` Mania Rating Scale total scores (r = 0.466, p < 0.01). CONCLUSION: The study demonstrated distinct NH values in the FPN could serve as a valuable neuroimaging biomarker capable of differentiating patients with BipM and rBD, and NH values of the left MFG as a potential predictor of early treatment response in patients with BipM.
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OBJECTIVES: To investigate the changes in sleep quality, heart rate variability (HRV) and resting-state electroencephalogram (rsEEG) in patients with major depressive disorder (MDD), and to explore whether HRV and rsEEG may be served as more convenient tools to assess sleep quality in MDD patients. METHOD: We included a total of 91 subjects (46 healthy controls and 45 MDD patients) and compared their sleep quality, HRV and power spectra of rsEEG. Correlation analyses were conducted to discuss the relationship between HRV and seven factors of PSQI. Multiple linear regression model was used to examine whether absolute band power could predict sleep quality in MDD patients. RESULTS: We found higher PSQI scores and lower levels of HRV in depressive individuals compared with healthy controls. In MDD patients, sleep latency was negatively correlated with RMSSD and HF. Delta, theta, and alpha band power of rsEEG were higher in MDD patients. Regression analyses showed delta band power of TP8, as well as theta, alpha band power of AF3 predicts PSQI score of MDD patients. CONCLUSIONS: The findings of our study show that some aspects of sleep problems had negative correlations with parasympathetic activity and the regression model supports that the band power of rsEEG may be used as a potential indicator to evaluate the sleep quality in MDD patients. SIGNIFICANCE: Cortical hyperarousal may be one of the reasons leading to poor sleep quality of MDD patients. And resting-state EEG can be used as a potential indicator for clinical assessment of MDD patients' sleep quality.
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Trastorno Depresivo Mayor , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastorno Depresivo Mayor/complicaciones , Calidad del Sueño , Electroencefalografía , Análisis de Regresión , Frecuencia Cardíaca/fisiologíaRESUMEN
Introduction: The incidence of hospital-acquired pneumonia (HAP) is high in the medical setting for mental disorders. To date, effective measurements for preventing HAP in hospitalized mental disorder patients are unavailable. Methods: This study was conducted at the Large-Scale Mental Health Center of Renmin Hospital of Wuhan University (Wuhan, China) in two phases: baseline phase (January 2017-December 2019) and intervention phase (May 2020-April 2022). In the intervention phase, the HAP bundle management strategy was implemented in the Mental Health Center, and the data on HAP were collected continuously for analysis. Results: A total of 18,795 and 9,618 patients were included in the baseline and intervention phases, respectively. The age, gender, ward admitted to, type of mental disorder, and Charlson comorbidity index did not differ significantly. After intervention, the rate of HAP occurrence decreased from 0.95 to 0.52% (P < 0.001). Specifically, the HAP rate decreased from 1.70 to 0.95% (P = 0.007) in the closed ward and from 0.63 to 0.35% (P = 0.009) in the open ward. The HAP rate in the subgroups was higher in patients with schizophrenia spectrum disorders (1.66 vs. 0.74%) and organic mental disorders (4.92 vs. 1.41%), and in those ≥65 years old (2.82 vs. 1.11%) but decreased significantly after intervention (all P < 0.05). Conclusion: The implementation of the HAP bundle management strategy reduced the occurrence of HAP in hospitalized patients with mental disorders.