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Objective@#Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. @*Methods@#Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. @*Results@#Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC’s mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. @*Conclusion@#Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.
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Objective@#: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. @*Methods@#: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. @*Results@#: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. @*Conclusion@#: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.
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Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes.We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.
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Objective@#Mental health problems such as anxiety, panic, and depression have been exacerbated by the coronavirus disease-2019 (COVID-19). This study aimed to compare the symptom severities and overall function before and during the COVID-19 pandemic among patients with panic disorder (PD) seeking treatment compared to healthy controls (HCs). @*Methods@#Baseline data were collected from the two groups (patients with PD and HCs) in two separate periods: before COVID-19 (Jan 2016–Dec 2019) and during COVID-19 (Mar 2020–Jul 2022). A total 453 participants (before COVID-19: 246 [139 patients with PD and 107 HCs], during COVID-19: 207 [86 patients with PD and 121 HCs]) was included. Scales for panic and depressive symptoms and overall function were administered. Additionally, network analyses were performed to compare the two groups within the patients with PD. @*Results@#The results of two-way analysis of variance analyses showed that patients with PD enrolled during COVID-19 showed higher levels of interoceptive fear and lower overall functioning. In addition, a network comparison test revealed that a significantly high strength and expected influence for agoraphobia and avoidance in patients with PD during COVID-19. @*Conclusion@#This study suggested that the overall function could have worsened, and the importance of agoraphobia and avoidance as a central symptom may have increased in patients with PD seeking treatment during COVID-19.
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Objective@#This study investigated the effect of TNF-α rs1800629 polymorphism on white matter integrity and memory function in patients with schizophrenia. @*Methods@#Fifty-five participants with schizophrenia were enrolled in this study. They were genotyped for TNF-α rs1800629 polymorphism and underwent diffusion tensor imaging. Memory function was assessed using the Rey–Kim memory test. Participants with schizophrenia were grouped into GG homozygotes and A-allele carriers. @*Results@#Compared to GG homozygotes, A-allele carriers had significantly lower scores for immediate and delayed recall and recognition of verbal memory and showed significantly lower fractional anisotropy in extensive brain regions. Lower total scores in immediate and delayed recall of verbal memory, immediate recall of visual memory, and figure copy of visual memory were significantly correlated with decreased mean fractional anisotropy in the white matter tracts of the corresponding brain regions. @*Conclusion@#Our findings suggest that the A-allele, which is associated with higher levels of TNF-α expression, correlates with lower connectivity of the fronto-temporal white matter compared to that in GG homozygotes. Impaired fronto-temporal connectivity may be associated with genetic vulnerability to schizophrenia, leading to verbal and visual memory deficits in patients with schizophrenia.
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Objective@#The Reading the Mind in the Eyes Test (RMET) was developed by using Caucasian eyes, which may not be appropriate to be used in Korean. The aims of the present study were 1) to develop a Korean version of the RMET (K-RMET) by using Korean eye stimuli and 2) to examine the psychometric properties of the Korean-translated version of the RMET and the K-RMET. @*Methods@#Thirty-six photographs of Korean eyes were selected. A total of 196 (101 females) healthy subjects were asked to take the Korean-translated version of the RMET and K-RMET. To assess internal consistency reliability, Cronbach’s alpha coefficients were computed, and test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Confirmatory factor analysis (CFA) and item analysis were also conducted. @*Results@#Internal consistency, measured by Cronbach’s alpha, was 0.542 for the Korean-translated version of the RMET, and 0.540 for the K-RMET. Test–retest reliability (n=25), measured by the ICC, was 0.787 for the Korean-translated version of the RMET, and 0.758 for the K-RMET. In CFA, the assumed single and 3-factor model fit indices were not good in the both types of RMETs. There was difficulty in discrimination in nine items of the Korean-translated version of the RMET and 10 items of the K-RMET. @*Conclusion@#The psychometric properties of both the Korean-translated version of the RMET and the K-RMET are acceptable. Both tests are applicable to the clinical population, as well as the general population in Korea.
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Astrocytes play various important roles such as maintaining brain homeostasis, supporting neurons, and secreting inflammatory mediators to protect the brain cells. In aged subjects, astrocytes show diversely changed phenotypes and dysfunctions. But, the study of aged astrocytes or astrocytes from aged subjects is not yet sufficient to provide a comprehensive understanding of their important processes in the regulation of brain function. In this study, we induced an in vitro aged astrocyte model through late passage cultivation of rat primary cultured astrocytes. Astrocytes were cultured until passage 7 (P7) as late passage astrocytes and compared with passage 1 (P1) astrocytes as early passage astrocytes to confirm the differences in phenotypes and the effects of serial passage. In this study, we confirmed the morphological, molecular, and functional changes of late passage astrocytes showing aging phenotypes through SA-β-gal staining and measurement of nuclear size. We also observed a reduced expression of inflammatory mediators including IL-1β, IL-6, TNFα, iNOS, and COX2, as well as dysregulation of wound-healing, phagocytosis, and mitochondrial functions such as mitochondrial membrane potential and mitochondrial oxygen consumption rate. Cultureconditioned media obtained from P1 astrocytes promoted neurite outgrowth in immature primary cultures of rat cortices, which is significantly reduced when we treated the immature neurons with the culture media obtained from P7 astrocytes. These results suggest that late passage astrocytes show senescent astrocyte phenotypes with functional defects, which makes it a suitable model for the study of the role of astrocyte senescence on the modulation of normal and pathological brain aging.
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Objective@#Although neural correlates of sub-clinical agoraphobia (AG) symptoms have been previously suggested, only a few studies evaluating structural changes of the brain have been conducted in agoraphobic patients with panic disorder (PD). We investigated and compared white matter (WM) micro-structural alterations between PD patients with AG (PD + AG) and those without AG (PD − AG). @*Methods@#Our study included 56 female PD patients, of which 25 were diagnosed with AG and 31 were diagnosed without AG. Diffusion tensor imaging was performed to investigate micro-structural changes in the WM tracts related to fronto-temporo-occipital areas (uncinate fasciculus, cingulum bundle, inferior longitudinal/fronto-occipital fasciculus, fornix column and body, and fornix/stria terminalis). All participants were subjected to the Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory-II (BDI-II), and Albany Panic and Phobia questionnaires. @*Results@#The fractional anisotropy values of the right uncinate fasciculus in PD + AG were significantly lower than that of PD − AG and showed significant correlations with BDI-II and ASI-R total scores. Mean diffusivity and radial diffusivity values of the right uncinate fasciculus were significantly higher in PD + AG as compared to PD − AG. @*Conclusion@#Our findings suggest that the uncinate fasciculus may be associated with AG symptoms in PD, possibly through demyelination. Our findings may contribute to the neurobiological evidence regarding the association between AG and WM structural changes in PD.
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Objective@#The Reading the Mind in the Eyes Test (RMET) was developed by using Caucasian eyes, which may not be appropriate to be used in Korean. The aims of the present study were 1) to develop a Korean version of the RMET (K-RMET) by using Korean eye stimuli and 2) to examine the psychometric properties of the Korean-translated version of the RMET and the K-RMET. @*Methods@#Thirty-six photographs of Korean eyes were selected. A total of 196 (101 females) healthy subjects were asked to take the Korean-translated version of the RMET and K-RMET. To assess internal consistency reliability, Cronbach’s alpha coefficients were computed, and test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Confirmatory factor analysis (CFA) and item analysis were also conducted. @*Results@#Internal consistency, measured by Cronbach’s alpha, was 0.542 for the Korean-translated version of the RMET, and 0.540 for the K-RMET. Test–retest reliability (n=25), measured by the ICC, was 0.787 for the Korean-translated version of the RMET, and 0.758 for the K-RMET. In CFA, the assumed single and 3-factor model fit indices were not good in the both types of RMETs. There was difficulty in discrimination in nine items of the Korean-translated version of the RMET and 10 items of the K-RMET. @*Conclusion@#The psychometric properties of both the Korean-translated version of the RMET and the K-RMET are acceptable. Both tests are applicable to the clinical population, as well as the general population in Korea.
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Objective@#Relationship between hair cortisol concentration (HCC) and stress-related psychological measures are inconclusive, possibly due to overlooked heterogeneity regarding childhood trauma and a lack of comprehensive research on stress-related psychological factors. This study aims to compare young adults without history of childhood trauma to young adults who experienced childhood trauma using HCC and various stress-related psychological factors, as well as investigate the impacts of childhood trauma on the association between HCC and stress-related psychological measures. @*Methods@#A total of 206 young, healthy adults were recruited. We divided participants into two groups depending on whether or not they had suffered moderate-to-severe childhood trauma (CT+ and CT-) and compared HCC and various stress-related psychological measures between groups. Using multiple linear regression analyses, we assessed the associations between HCC and stress-related psychological measures for each group. @*Results@#We found no difference between the groups in HCC or the reported number of stressful life events in the past year; however, CT+ individuals reported higher stress perception, more depressive and anxiety-related symptoms, and more difficulties in emotion regulation than CT- individuals. HCC was associated with emotion dysregulation among the CT- individuals, but not among the CT+ individuals. @*Conclusion@#These findings suggest that history of childhood trauma should be considered in studies using HCC as a biomarker for stress in young adults. Furthermore, HCC might be a useful biomarker of stress and stress-related emotion dysregulation in individuals without moderate-to-severe childhood trauma.
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Objective@#The Reading the Mind in the Eyes Test (RMET) is a common measure of the Theory of Mind. Previous studies found a correlation between RMET performance and neurocognition, especially reasoning by analogy; however, the nature of this relationship remains unclear. Additionally, neurocognition was shown to play a significant role in facial emotion recognition. This study is planned to examine the nature of relationship between neurocognition and RMET performance, as well as the mediating role of facial emotion recognition. @*Methods@#One hundred fifty non-clinical youths performed the RMET. Reasoning by analogy was tested by Raven’s Standard Progressive Matrices (SPM) and facial emotion recognition was assessed by the Korean Facial Expressions of Emotion (KOFEE) test. The percentile bootstrap method was used to calculate the parameters of the mediating effects of facial emotion recognition on the relationship between SPM and RMET scores. @*Results@#SPM scores and KOFEE scores were both statistically significant predictors of RMET scores. KOFEE scores were found to partially mediate the impact of SPM scores on RMET scores. @*Conclusion@#These findings suggested that facial emotion recognition partially mediated the relationship between reasoning by analogy and social cognition. This study highlights the need for further research for individuals with serious mental illnesses.
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Objective@#The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD. @*Methods@#Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics. @*Results@#The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II. @*Conclusion@#Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.
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Schizophrenia is a debilitating psychiatric disorder with a substantial socioeconomic and humanistic burden. Currently available treatment strategies mostly rely on antipsychotic drugs, which block dopaminergic effects in the mesolimbic pathway of the brain. Although antipsychotic drugs help relieve psychotic symptoms, a definitive cure for schizophrenia has yet to be achieved. Recent advances in neuroinflammation research suggest that proinflammatory processes in the brain could cause alterations in neurobehavioral development and increase vulnerability to schizophrenia. With a growing need for novel strategies in the treatment of schizophrenia, it would be meaningful to review the current evidence supporting the therapeutic potential of anti-inflammatory strategies. This review details the key findings of clinical trials that investigate the efficacy of anti-inflammatory agents as adjuvants to antipsychotic treatment. We further discuss the possibilities of repurposing anti-inflammatory agents and developing novel strategies for the treatment of schizophrenia.
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Objective@#Early trauma (ET) is widely recognized as a contributing factor to the development of panic disorder (PD) in patients. However, there is a dearth of research on the specific volumes of hippocampal subregions and their laterality with respect to ET and PD. @*Methods@#A total of 30 subjects with PD and 30 age- and sex-matched healthy controls (HCs) were included in this study. All the subjects were evaluated by 3T-magnetic resonance imaging. FreeSurfer version 6.0 was used for volumetric analysis of the hippocampal subregions and their laterality. A shortened version of the Early Trauma Inventory Self Report (ETISR) as well as Anxiety Sensitivity Inventory-Revised (ASI-R), and Panic Disorder Severity Scale were utilized for analysis. @*Results@#Multivariate analysis of variance showed that the volume of the right hippocampal tail and laterality indices (LIs) of the hippocampal body and tail were significantly larger in subjects with PD relative to HCs. The significance of the observations remained unchanged after multivariate analysis of covariance, controlling for age, sex, years of education, medication, depressive symptoms, and intracranial volume as covariates. The LIs of the hippocampal tails that showed a significant correlation to ETISR emotional and physical subscales were also associated with ASI-R for cardiovascular symptoms in PD. @*Conclusion@#Our study displayed an increased rightward lateralization of the hippocampal tails in subjects with PD compared with HCs. This alteration in the brain, which was associated with early emotional and physical trauma, would negatively affect anxiety sensitivity to cardiovascular symptoms in subjects with PD.
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OBJECTIVES: The objective of this study is to investigate differences in clinical characteristics between female panic disorder (PD) patients with abortion history (PD+A) and without abortion history (PD−A).METHODS: We examined data from 341 female patients diagnosed with PD. We divided the patients with PD into PD+A (82 patients) and PD−A (259 patients) to compare demographic and clinical characteristics. The following instruments were applied : stress coping strategies, NEO-neuroticism, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Depression Inventory, the Beck Anxiety Inventory (BAI) and the Sheehan Disability Scale.RESULTS: Compared to the PD−A, the PD+A group showed no significant difference in coping strategies. However, significantly higher scores in neuroticism, the ASI-R, the APPQ and the BAI were observed. In terms of health-related disability, the PD+A group did not show significant difference.CONCLUSIONS: Our results suggest that the PD+A group may differ from the PD−A group in trait markers such as neuroticism and anxiety sensitivity, and abortion history may be associated with panic-related symptom severity. Our study suggests that further consideration is needed on such clinical characteristics in PD patients with abortion history.
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Femenino , Humanos , Aborto Inducido , Ansiedad , Depresión , Trastorno de Pánico , Pánico , Trastornos FóbicosRESUMEN
Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.
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Humanos , Agresión , Antipsicóticos , Catecol O-Metiltransferasa , Clozapina , Comorbilidad , Crimen , Neuroimagen , Regiones Promotoras Genéticas , Factores de Riesgo , Esquizofrenia , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Trastornos Relacionados con Sustancias , ViolenciaRESUMEN
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence-associated β-galactosidase (SA-β-gal) activity. Tenovin-1-treated astrocytes showed increased SA-β-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-1β, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.
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Animales , Ratas , Envejecimiento , Astrocitos , Barrera Hematoencefálica , Encéfalo , Senescencia Celular , Recuento de Células , Puntos de Control del Ciclo Celular , Interleucina-6 , Lenguaje , Memoria , Enfermedades Neurodegenerativas , Neuronas , Permeabilidad , Fenotipo , Cicatrización de HeridasRESUMEN
Brain aging is an inevitable process characterized by structural and functional changes and is a major risk factor for neurodegenerative diseases. Most brain aging studies are focused on neurons and less on astrocytes which are the most abundant cells in the brain known to be in charge of various functions including the maintenance of brain physical formation, ion homeostasis, and secretion of various extracellular matrix proteins. Altered mitochondrial dynamics, defective mitophagy or mitochondrial damages are causative factors of mitochondrial dysfunction, which is linked to age-related disorders. Etoposide is an anti-cancer reagent which can induce DNA stress and cellular senescence of cancer cell lines. In this study, we investigated whether etoposide induces senescence and functional alterations in cultured rat astrocytes. Senescence-associated β-galactosidase (SA-β-gal) activity was used as a cellular senescence marker. The results indicated that etoposide-treated astrocytes showed cellular senescence phenotypes including increased SA-β-gal-positive cells number, increased nuclear size and increased senescence-associated secretory phenotypes (SASP) such as IL-6. We also observed a decreased expression of cell cycle markers, including Phospho-Histone H3/Histone H3 and CDK2, and dysregulation of cellular functions based on wound-healing, neuronal protection, and phagocytosis assays. Finally, mitochondrial dysfunction was noted through the determination of mitochondrial membrane potential using tetramethylrhodamine methyl ester (TMRM) and the measurement of mitochondrial oxygen consumption rate (OCR). These data suggest that etoposide can induce cellular senescence and mitochondrial dysfunction in astrocytes which may have implications in brain aging and neurodegenerative conditions.
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Animales , Ratas , Envejecimiento , Astrocitos , Encéfalo , Senescencia Celular , Ciclo Celular , Línea Celular , ADN , Etopósido , Proteínas de la Matriz Extracelular , Homeostasis , Interleucina-6 , Potencial de la Membrana Mitocondrial , Mitocondrias , Mitofagia , Dinámicas Mitocondriales , Enfermedades Neurodegenerativas , Neuronas , Neuroprotección , Consumo de Oxígeno , Fagocitosis , Fenotipo , Factores de Riesgo , Cicatrización de HeridasRESUMEN
OBJECTIVES: Disrupted integrities of the fornix and stria terminalis have been suggested in schizophrenia. However, very few studies have focused on the fornix and stria terminalis comparing first-episode schizophrenia (FESZ), chronic schizophrenia (CS), and healthy controls (HCs) with the application of diffusion-tensor imaging (DTI) technique. The objective of this study is to compare the connectivity of the fornix and stria terminalis among FESZ, CS, and HCs. METHODS: We included the 44 FESZ patients, 39 CS patients and 20 HCs in this study. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics to analyze the connectivity of fornix and stria terminalis. In addition, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate clinical symptom severities. RESULTS: There were no significant differences between the FESZ, CS, and HCs in age, sex, education years. The SAPS and SANS scores of the schizophrenia groups showed no significant differences. FA values of the right fornix cres/stria terminalis in the CS group were significantly lower than those in FESZ and HCs. There were no significant differences of FA values of the right fornix cres/stria terminalis between the FESZ and the HCs. Pearson correlation analyses revealed that significant correlation between FA values of the right fornix cres/stria terminalies of the the FESZ group and positive, negative symptom scales, and FA values of the right fornix cres/stria terminalis of the CS group and negative symptom scales. CONCLUSIONS: This study shows that FA values of the fornix and stria terminalis in the CS were lower than in the FESZ and the HCs. These results suggest that the fornix and stria terminalis can play a role in pathophysiology of schizophrenia. Thus current study can broaden our understanding of the pathophysiology of schizophrenia.
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Humanos , Anisotropía , Educación , Fórnix , Esquizofrenia , Núcleos Septales , Pesos y Medidas , Sustancia BlancaRESUMEN
Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives. In this study, we investigated the effects of benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea on ROS-dependent apoptosis of rat neural progenitor cells (NPCs) in vitro. Cells were isolated and cultured from embryonic day 14 rat cortices. Cultured cells were treated with 1–1,000 nM benzalkonium chloride, and 1–50 μM diazolidinyl urea or imidazolidinyl urea at various time points to measure the reactive oxygen species (ROS). PI staining, MTT assay, and live-cell imaging were used for cell viability measurements. Western blot was carried out for cleaved caspase-3 and cleaved caspase-8 as apoptotic protein markers. In rat NPCs, ROS production and cleaved caspase-8 expression were increased while the cell viability was decreased in high concentrations of these substances. These results suggest that several cosmetic preservatives at high concentrations can induce neural toxicity in rat brains through ROS induction and apoptosis.