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Multimorbidity is a healthcare concern. To manage diseases, older adults with multimorbidity are expected to practice health behaviors, particularly medication adherence. Studies have examined adherence issues in older patients with multiple diseases, but it remains unclear which factors affect medication adherence. Therefore, this study aimed to identify the factors affecting medication adherence among older adults with multimorbidity. The participants were recruited from the outpatient departments of two hospitals in the Republic of Korea using convenience sampling. Data were collected using structured questionnaires and analyzed using multiple regression analysis. The results showed that those with a lower education level, no side effects, better health literacy, higher medication self-efficacy, and more social support exhibited better medication adherence. In addition, beliefs about medication were not related to medication adherence. These results suggest that providing individualized education, strengthening social support, and decreasing harmful side effects can improve medication adherence.
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Adesão à Medicação , Multimorbidade , Humanos , Idoso , Estudos Transversais , Inquéritos e Questionários , Projetos de PesquisaRESUMO
Based on our previous report that 3-morpholino-1-phenylpropan-1-one 2, one of the fluoxetine's simplified morpholino analogue, inhibited nitric oxide (NO) production, in this paper, various substituted benzene analogues with morpholine hydrochloride of 2 were synthesized and their inhibitory effects on NO production in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 2-trifluoromethyl analogue 16n (IC50 = 8.6 µM) showed a significantly higher inhibitory activity than that of the parent compound 2a (IC50 > 50 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 16n also inhibited iNOS expression in LPS-induced BV2 cells at 2, 10 and 20 µM concentrations. These results suggest that compound 16n inhibited NO production by suppressing the expression of iNOS and can be used as a lead structure for developing new inhibitor of NO production.
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Cloretos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Morfolinas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Animais , Linhagem Celular , Cloretos/síntese química , Cloretos/química , Relação Dose-Resposta a Droga , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Morfolinas/síntese química , Morfolinas/química , Óxido Nítrico/biossíntese , Relação Estrutura-AtividadeRESUMO
In-Situ catalytic pyrolysis of dealkaline lignin (DL) over MMZ-Hß was performed using a pyrolyzergas chromatography/mass spectroscopy for the first time. Non-catalytic pyrolysis of DL mainly produced large amounts of phenolics such as mono-phenol, alkylphenols, guaiacols, eugenols, and vanillin. By applying MMZ-Hß, the amounts of these phenolics were dramatically decreased with the increase of aromatics such as benzene, toluene, ethylbenzene, xylenes, and naphthalenes. The higher conversion efficiency from phenolics to aromatics was obtained by increasing the catalyst to DL ratio from 1/1 to 5/1.
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The therapeutic efficacy of intranasal iNOS siRNA delivery was investigated in the postischemic rat brain after encapsulating on in gelatin nanoparticles (GNPs; diameter 188.0 ± 60.9 nm) cross-linked with 0.0667% glutaraldehyde (GA). Intranasally delivered GNPs were found in extracellular and intracellular compartments of many brain regions, including the olfactory bulb, cerebral cortex, and striatum at 1 hour after infusion and continued to be detected for days. Infarct volumes were markedly suppressed (maximal reduction to 42.1 ± 2.6%) at 2 days after 60 minutes of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hours post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for 2 weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect.
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Nanopartículas , Fármacos Neuroprotetores/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Administração Intranasal , Animais , Encéfalo , Gelatina , Infarto da Artéria Cerebral Média/tratamento farmacológico , RatosRESUMO
Physical exercise is considered beneficial in the treatment of depression, but the underlying mechanism is not clearly understood. In the present study, we investigated the mechanism regulating antidepressant effects of exercise by focusing on the role of the amygdala using a well-defined animal model of depression. C57BL/6 mice treated with repeated restraint showed depression-like behaviors, which was counteracted by post-stress treatment with physical exercise. The two neuropeptides hypocretin/orexin (Hcrt/Orx) and melanin-concentrating hormone (MCH) were transcriptionally upregulated in the BLA after repeated stress, and their enhanced expression was downregulated by treatment with exercise, mirroring stress-induced depression-like behaviors and their reversal by exercise. Stereotaxic injection of either Hcrt/Orx peptide or MCH peptide within the BLA commonly increased phospho-CaMKIIα level and produced depression-like behaviors, mimicking the neural states in the BLA of mice subjected to repeated stress. In contrast, siRNA-mediated suppression of Hcrt/Orx or MCH in the BLA blocked stress-induced depression-like behaviors. Furthermore, siRNA-mediated inhibition of CaMKIIα in the BLA also counteracted stress-induced depression-like behaviors. Local injection of Hcrt/Orx peptide or MCH peptide within the BLA in exercise-treated animals blocked antidepressant-like effects of exercise. Together these results suggest that exercise produces antidepressant effects via suppression of Hcrt/Orx and MCH neural systems in the BLA.
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Complexo Nuclear Basolateral da Amígdala/fisiopatologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Orexinas/metabolismo , Hormônios Hipofisários/metabolismo , Corrida/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Doença Crônica , Modelos Animais de Doenças , Feminino , Hormônios Hipotalâmicos/genética , Masculino , Melaninas/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Orexinas/genética , Condicionamento Físico Animal , Hormônios Hipofisários/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Restrição Física , Estresse Psicológico/fisiopatologiaRESUMO
HMGB1 is a prototypical danger-associated molecular pattern (DAMP) molecule that co-localizes with amyloid beta (Aß) in the brains of patients with Alzheimer's disease. HMGB1 levels are significantly higher in the cerebrospinal fluid of patients. However, the cellular and subcellular distribution of HMGB1 in relation to the pathology of Alzheimer's disease has not yet been studied in detail. Here, we investigated whether HMGB1 protein levels in brain tissue homogenates (frontal cortex and striatum) and sera from Tg-APP/PS1 mice, along with its cellular and subcellular localization in those regions, differed. Total HMGB1 levels were increased in the frontal cortices of aged wildtype (7.5 M) mice compared to young (3.5 M) mice, whereas total HMGB1 levels in the frontal cortices of Tg-APP/PS1 mice (7.5 M) were significantly lower than those in age-matched wildtype mice. In contrast, total serum HMGB1 levels were enhanced in aged wildtype (7.5 M) mice and Tg-APP/PS1 mice (7.5 M). Further analysis indicated that nuclear HMGB1 levels in the frontal cortices of Tg-APP/PS1 mice were significantly reduced compared to those in age-matched wildtype controls, and cytosolic HMGB1 levels were also significantly decreased. Triple-fluorescence immunohistochemical analysis indicated that HMGB1 appeared as a ring shape in the cytoplasm of most neurons and microglia in the frontal cortices of 9.5 M Tg-APP/PS1 mice, indicating that nuclear HMGB1 is reduced by aging and in Tg-APP/PS1 mice. Consistent with these observations, Aß treatment of both primary cortical neuron and primary microglial cultures increased HMGB1 secretion in the media, in an Aß-dose-dependent manner. Our results indicate that nuclear HMGB1 might be translocated from the nucleus to the cytoplasm in both neurons and microglia in the brains of Tg-APP/PS1 mice, and that it may subsequently be secreted extracellularly.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Proteína HMGB1 , Idoso , Animais , Humanos , Camundongos , Alarminas , Encéfalo , Microglia , Neurônios , Modelos Animais de DoençasRESUMO
Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of "responses to stress or steroid hormones", "histone modification", and "regulating MAPK signaling pathways". While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.
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BACKGROUND: Mindfulness-based training programs have consistently shown efficacy in stress reduction. However, questions regarding the optimal duration and most effective delivery methods remain. OBJECTIVE: This research explores a 4-week neurofeedback-assisted mindfulness training for employees via a mobile app. The study's core query is whether incorporating neurofeedback can amplify the benefits on stress reduction and related metrics compared with conventional mindfulness training. METHODS: A total of 92 full-time employees were randomized into 3 groups: group 1 received mobile mindfulness training with neurofeedback assistance (n=29, mean age 39.72 years); group 2 received mobile mindfulness training without neurofeedback (n=32, mean age 37.66 years); and group 3 were given self-learning paper materials on stress management during their first visit (n=31, mean age 38.65 years). The primary outcomes were perceived stress and resilience scales. The secondary outcomes were mindfulness awareness, emotional labor, occupational stress, insomnia, and depression. Heart rate variability and electroencephalography were measured for physiological outcomes. These measurements were collected at 3 different times, namely, at baseline, immediately after training, and at a 4-week follow-up. The generalized estimating equation model was used for data analysis. RESULTS: The 4-week program showed significant stress reduction (Wald χ22=107.167, P<.001) and improvements in psychological indices including resilience, emotional labor, insomnia, and depression. A significant interaction was observed in resilience (time × group, Wald χ42=10.846, P=.02). The post hoc analysis showed a statistically significant difference between groups 1 (least squares mean [LSM] 21.62, SE 0.55) and 3 (LSM 19.90, SE 0.61) at the posttraining assessment (P=.008). Group 1 showed a significant improvement (P<.001) at the posttraining assessment, with continued improvements through the 1-month follow-up assessment period (LSM 21.55, SE 0.61). Physiological indices were analyzed only for data of 67 participants (22 in group 1, 22 in group 2, and 23 in group 3) due to the data quality. The relaxation index (ratio of alpha to high beta power) from the right electroencephalography channel showed a significant interaction (time × group, Wald χ22=6.947, P=.03), with group 1 revealing the highest improvement (LSM 0.43, SE 0.15) compared with groups 2 (LSM -0.11, SE 0.10) and 3 (LSM 0.12, SE 0.10) at the 1-month follow-up assessment. CONCLUSIONS: The study demonstrated that the neurofeedback-assisted group achieved superior outcomes in resilience and relaxation during the 4-week mobile mindfulness program. Further research with larger samples and long-term follow-up is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03787407; https://clinicaltrials.gov/ct2/show/NCT03787407.
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Atenção Plena , Aplicativos Móveis , Neurorretroalimentação , Estresse Ocupacional , Distúrbios do Início e da Manutenção do Sono , Humanos , Adulto , Atenção Plena/métodos , Estresse Ocupacional/terapia , Estresse Ocupacional/psicologiaRESUMO
[This corrects the article on p. 71 in vol. 32, PMID: 33828406.].
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Mounting evidence suggests that probiotics are beneficial for treating Alzheimer's disease (AD). However, the mechanisms by which specific probiotics modify AD pathophysiology are not clearly understood. In this study, we investigated whether Lactobacillus paracasei-derived extracellular vesicles (Lpc-EV) can directly act on neuronal cells to modify amyloid-beta (Aß)-induced transcriptional changes and Aß pathology in the brains of Tg-APP/PS1 mice. Lpc-EV treatment in HT22 neuronal cells counteracts Aß-induced downregulation of Brain-derived neurotrophic factor (Bdnf), Neurotrophin 3 (Nt3), Nt4/5, and TrkB receptor, and reverses Aß-induced altered expression of diverse nuclear factors, including the downregulation of Methyl-CpG binding protein 2 (Mecp2) and Sirtuin 1 (Sirt1). Systematic siRNA-mediated knockdown experiments indicate that the upregulation of Bdnf, Nt3, Nt4/5, and TrkB by Lpc-EV is mediated via multiple epigenetic factors whose activation converges on Mecp2 and Sirt1. In addition, Lpc-EV reverses Aß-induced downregulation of the Aß-degrading proteases Matrix metalloproteinase 2 (Mmp-2), Mmp-9, and Neprilysin (Nep), whose upregulation is also controlled by MeCP2 and Sirt1. Lpc-EV treatment restores the downregulated expression of Bdnf, Nt4/5, TrkB, Mmp-2, Mmp-9, and Nep; induces the upregulation of MeCP2 and Sirt1 in the hippocampus; alleviates Aß accumulation and neuroinflammatory responses in the brain; and mitigates cognitive decline in Tg-APP/PS1 mice. These results suggest that Lpc-EV cargo contains a neuroactive component that upregulates the expression of neurotrophic factors and Aß-degrading proteases (Mmp-2, Mmp-9, and Nep) through the upregulation of MeCP2 and Sirt1, and ameliorates Aß pathology and cognitive deficits in Tg-APP/PS1 mice.
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Doença de Alzheimer , Vesículas Extracelulares , Camundongos , Animais , Metaloproteinase 2 da Matriz/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Regulação para Cima , Lactobacillus/metabolismo , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Endopeptidases/metabolismo , Vesículas Extracelulares/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animais de Doenças , Presenilina-1/genéticaRESUMO
C-reactive protein (CRP) or procalcitonin (PCT) alone has limitations in the early detection of infection or inflammation due to shortcomings in specificity and varied cut-off values. Recently, interleukin (IL)-6 has been assessed, but it is not known to what extent the three values are homogeneous in reality. This retrospective study was conducted with two large datasets (discrepancy set with results within 24 h of admission [7149 patients] and follow-up set until 2 weeks of hospital stay [5261 tests]) consisting of simultaneous examinations of CRP, PCT, and IL-6 between January 2015 and August 2021. The specific discrepant group (n = 102, 1.4%) with normal CRP (<10 mg/L) and PCT (<0.1 ng/mL) and high IL-6 (≥100 pg/mL) values was extracted from the discrepancy set. Dimensionality reduction and visualization were performed using Python. The three markers were not clearly clustered after t-distributed stochastic neighbor embedding. Pearson's correlation coefficients between two markers were substantially low (0.23−0.55). Among the high normalized IL-6 levels (≥0.5) (n = 349), 17.8% and 38.7% of CRP and PCT levels were very low (≤0.01). 9.2% and 13.4% of normal CRP (n = 1522) had high PCT (≥0.5 ng/mL) and IL-6 (≥100 pg/mL) values, respectively. Infection and bacteremia among 102 patients occurred in 36 (35.3%) and 9 (8.8%) patients, respectively. In patients with bacteremia, IL-6 was the first to increase, followed by PCT and CRP. Our study revealed that CRP, PCT, and IL-6 levels were considerably discrepant, which could be misinterpreted if only CRP tests are performed.
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BACKGROUND: The reward system regulates motivated behavior, and repeated practice of specific motivated behavior might conversely modify the reward system. However, the detailed mechanisms by which they reciprocally regulate each other are not clearly understood. METHODS: Mice subjected to chronic restraint stress show long-lasting depressive-like behavior, which is rescued by continual engagement with playable objects. A series of molecular, pharmacological, genetic, and behavioral analyses, combined with microarray, liquid chromatography, and chemogenetic tools, are used to investigate the neural mechanisms of antidepressive effects of playable objects. RESULTS: Here, we show that repeated restraint induces dopamine surges into the nucleus accumbens-lateral shell (NAc-lSh), which cause upregulation of the neuropeptide PACAP in the NAc-lSh. As repeated stress is continued, the dopamine surge by stressors is adaptively suppressed without restoring PACAP upregulation, and the resulting enhanced PACAP inputs from NAc-lSh neurons to the ventral pallidum facilitate depressive-like behaviors. Continual engagement with playable objects in mice subjected to chronic stress remediates reduced dopamine response to new stressors, enhanced PACAP upregulation, and depressive-like behaviors. Overactivation of dopamine D1 receptors over the action of D2 receptors in the NAc-lSh promotes depressive-like behaviors. Conversely, inhibition of D1 receptors or PACAP upregulation in the NAc-lSh confers resilience to chronic stress-induced depressive-like behaviors. Histochemical and chemogenetic analyses reveal that engagement with playable objects produces antidepressive effects by reshaping the ventral tegmental area-to-NAc-lSh and NAc-lSh-to-ventral pallidum circuits. CONCLUSIONS: These results suggest that behavioral engagement with playable objects remediates depressive-like behaviors by resolving stress-induced maladaptive changes in the reward system.
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Dopamina , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Animais , Antidepressivos/farmacologia , Camundongos , Núcleo Accumbens , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Recompensa , Área Tegmentar VentralRESUMO
Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
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Agressão/fisiologia , Transtorno Depressivo/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/fisiopatologia , Agressão/psicologia , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Corticosterona/farmacologia , Transtorno Depressivo/psicologia , Feminino , Perfilação da Expressão Gênica/métodos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Restrição Física , Fatores de TempoRESUMO
OBJECTIVES: This study was conducted to investigate the reliability and validity of the Korean version of the DSM-5 Level 2 Cross-Cutting Symptom Measure-inattention [Swanson, Nolan and Pelham, version IV (SNAP-IV)] and anger [Patient-Reported Outcome Measurement Information System (PROMIS) Anger] for parents and guardians of children aged 6-17 years. METHODS: We included 104 children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD), ADHD with anxiety and depression, depressive disorder, anxiety disorder, and tic disorder with somatic symptoms (ADHD=41, depression=9, anxiety=14, ADHD+anxious depression=11, tic+somatic symptoms=29). Their ages ranged from 8 years to 15 years. The participants' mothers completed the SNAP-IV, PROMIS Anger scale, Korean version of the IOWA Conners Rating Scale (K-IOWA), and Korean ADHD Rating Scale (K-ARS) so that the reliability and validity of the SNAP-IV and PROMIS Anger scales, which are DSM-5 scales for assessing inattention and anger of children and adolescents, could be examined. RESULTS: The reliability coefficient of SNAP-IV (Cronbach's α) was 0.94. The correlation coefficients between SNAP-IV, K-IOWA inattention, and K-ARS inattention scores ranged from 0.73 to 0.86. The mean SNAP-IV scores of the ADHD and the ADHD+anxious depression groups were significantly higher than those of the anxiety and the tic+somatic symptoms groups. The reliability coefficient of the PROMIS Anger was 0.91. The correlation coefficient between PROMIS Anger and K-IOWA oppositional/defiant scores was 0.75. The PROMIS Anger mean score of the ADHD+anxious depression group tended to be higher than that of the other groups. CONCLUSION: These results suggest that the Korean version of the DSM-5 Level 2 Cross-Cutting Symptom Measure-inattention and anger for parent and guardian of child age 6-17 might be a reliable and valid test and may be useful for screening children and adolescents with ADHD.
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The monoamine hypothesis of depression, namely that the reduction in synaptic serotonin and dopamine levels causes depression, has prevailed in past decades. However, clinical and preclinical studies have identified various cortical and subcortical regions whose altered neural activities also regulate depressive-like behaviors, independently from the monoamine system. Our systematic review indicates that neural activities of specific brain regions and associated neural circuitries are adaptively altered after chronic stress in a specific direction, such that the neural activity in the infralimbic cortex, lateral habenula and amygdala is upregulated, whereas the neural activity in the prelimbic cortex, hippocampus and monoamine systems is downregulated. The altered neural activity dynamics between monoamine systems and cortico-limbic systems are reciprocally interwoven at multiple levels. Furthermore, depressive-like behaviors can be experimentally reversed by counteracting the altered neural activity of a specific neural circuitry at multiple brain regions, suggesting the importance of the reciprocally interwoven neural networks in regulating depressive-like behaviors. These results promise for reshaping altered neural activity dynamics as a therapeutic strategy for treating depression.
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Monoaminas Biogênicas/metabolismo , Córtex Cerebral/fisiopatologia , Depressão/metabolismo , Transtorno Depressivo/metabolismo , Sistema Límbico/fisiopatologia , Neurônios/metabolismo , Estresse Psicológico/metabolismo , Animais , Córtex Cerebral/metabolismo , Depressão/etiologia , Transtorno Depressivo/etiologia , Modelos Animais de Doenças , Humanos , Sistema Límbico/metabolismo , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Estresse Psicológico/complicações , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/fisiopatologiaRESUMO
We developed sociability tests based on use of a U-shaped two-choice field to read out behavioral states of sociability in rodents. The U-shaped two-choice field is a modified open field that is partially partitioned with a wall projecting to the central point, resulting in two symmetrical rectangular fields, each containing closed and open square zones that together form a 'U-shaped field'. The U-shaped two-choice field can be used to measure animal's behavioral responses to two contrasting or similar options, such as (i) a social target versus an inanimate object, (ii) a new stranger versus an earlier stranger, and (iii) a novel animal (a non-mate) versus a cage-mate (a familiar animal). We describe detailed procedures for sociability tests for the above three behavioral test paradigms based on the U-shaped two-choice field.
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A new species of arbuscular mycorrhizal fungi (Glomeromycota), Acaulospora koreana, was isolated from forest soils in South Korea. This novel fungus was collected from the rhizosphere of Lindera obtusiloba and Styrax obassia in forest and propagated with Sorghum bicolor in pot. Morphological characteristics of spores of A. koreana are rarely distinguished from Acaulospora mellea, which is reported as one of the most abundant mycorrhizal species in Korea. However, molecular evidence of rDNA sequence using improved primers for glomeromycotan fungal identification strongly supported that A. koreana is different from A. mellea but also any other species belonging to the genus Acaulospora. This is the first novel glomeromycatan fungus introduced in South Korea, but it suggests that there is a high possibility for discovering new arbuscular mycorrhizal fungi considering the abundance of plant species and advanced phylogenetic analysis technique.
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The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.
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Transtorno Autístico/metabolismo , Corpo Estriado/metabolismo , Receptores de Dopamina D1/metabolismo , Animais , Transtorno Autístico/patologia , Comportamento Animal , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Corpo Estriado/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Optogenética , Fosforilação , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Comportamento Social , Substância Negra/metabolismoRESUMO
We investigated the effects on various crops of inoculation with species of arbuscular mycorrhizal fungi (AMF) in soils from different sources and selected AMF species suitable for domestic environment-friendly farming. Effects on plants varied with the AMF species used. In carrot, Scutellospora heterogama, Acaulospora longula, and Funneliformis mosseae had a positive effect on growth of the host, whereas AMF had only weak effects on the growth of red pepper and leek. AMF inoculation had positive effects on the growth of carrot and sorghum. The results of this study indicate the nature of the relationship between soil, plants, and AMF; this study therefore has important implications for the future use of AMF in environment-friendly agriculture.
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Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.