• Herbal Formula Science
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• v.27 no.2
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• pp.121-136
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• 2019

Objective : To investigate the effect of sihogayonggolmoryeotang (SY) on Single Prolonged Stress(SPS)-induced Post Traumatic Stress Disorder(PTSD). Method : To confirm the effects of SY on SPS-induced PTSD, Changes in body weight, sucrose intake open field test(OFT) and forced swimming test(FST)were observed. After behavioral tests, the plasma corticosterone(CORT) from the abdominal aorta, serotonin(5-HT) from prefrontal cortex, hippocampus, amygdala and striatum, norepinephrine(NE) and dopamine(DA) from hippocampus was measured by ELISA. mRNA expression of brain-derived neurotrophic factor(BDNF) and cAMP response element-binding protein(CREB) in hippocampus was measured by RT-PCR. Result : Weight change and sucrose intakes of rats in 14th day after the administration of SY were significantly increased in the SPS + SY450 group compared to the SPS group (p<0.05). Numbers of crossing in the central zone in the OFT were significantly increased in the SPS + SY450 group (p<0.05) compared with the SPS group. The immobility time of FST was significantly decreased in SPS + SY450 group compared with SPS group (p<0.05). The change of plasma CORT concentration was significantly decreased in SPS + SY450 group compared with that in SPS group (p<0.05). The change of 5-HT concentration was significantly increased in the SPS + SY450 group at hippocampus and amygdala compared with the SPS group (p<0.05). The concentration of DA was significantly increased in the SPS + SY450 group compared with the SPS group (p<0.05). The expression of BDNF and CREB were significantly increased in SPS + SY450 group compared with the SPS group (p<0.05). Conclusion : SY administration lowered the increase of CORT caused by PTSD and increases the 5-HT concentration and reversed the decreased expression of NE and DA and BDNF and CREB by PTSD. It is postulated that SY is effective in treating PTSD by restoring cognitive function, memory impairment, unstable emotional disturbances.

• Anxiety and mood
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• v.15 no.2
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• pp.68-76
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• 2019

Objective : The goal of this study was to investigate the characteristics of early maladaptive schemas (EMSs), and associated neurocognitive functions as seen in visitors for military designation process. Methods : This retrospective study included 111 males aged 18 to 24 years among three groups: 41 visitors for military designation process (VMD), 21 patients with obsessive-compulsive disorder (OCD), and 49 healthy subjects. We collected the results of the Young Schema Questionnaire, Symptom Checklist-90-Revised, three neurocognitive tests as well as their clinicodemographic data. We analyzed the differences in EMSs between these three groups, and the correlations among the identified EMSs and neurocognitive performances within the VMD group. Results : Compared with both the OCD and healthy groups, the evaluation of the VMD group showed significantly higher scores in mistrust/abuse (F=6.4, p=0.002), vulnerability to harm (F=6.6, p<0.0001) and negativity/pessimism schema (F=7.3, p<0.0001), even when controlling for depression scores and levels of education. These three schemas also exhibited significant negative correlations with the score of Stroop test with r ranging from -0.34 to -0.44. Conclusion : These findings suggest that people who are likely to have difficulties adjusting to living in a military life may have psychological vulnerabilities related to certain EMSs. Further studies are warranted to test the clinical potentials of these findings, such as a treatment target and a predictor factor.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.168-177
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• 2019

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

• Journal of mucopolysaccharidosis and rare diseases
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• v.5 no.1
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• pp.17-21
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• 2021

Hunter syndrome or mucopolysaccharidosis type II (MPS-II) (OMIM 309900) is a rare lysosomal storage disorder caused by deficiency in the activity of the enzyme iduronate-2-sulfatase. This enzyme is responsible for the catabolism of the following two different glycosaminoglycans (GAGs): dermatan sulfate and heparan sulfate. The lysosomal accumulation of these GAG molecules results in cell, tissue, and organ dysfunction. Patients can be broadly classified as having one of the following two forms of MPS II: a severe form and an attenuated form. In the severe form of the disease, signs and symptoms (including neurological impairment) develop in early childhood, whereas in the attenuated form, signs and symptoms develop in adolescence or early adulthood, and patients do not experience significant cognitive impairment. The involvement of the skeletal-muscle system is because of essential accumulated GAGs in joints and connective tissue. MPS II has many clinical features and includes two recognized clinical entities (mild and severe) that represent two ends of a wide spectrum of clinical severities. However, enzyme replacement therapy is likely to have only a limited impact on bone and joint disease based on the results of MPS II studies. The aim of this study was to review the involvement of joints in MPS II.

• Journal of Biomedical Engineering Research
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• v.42 no.6
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• pp.295-303
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• 2021

Idiopathic normal-pressure hydrocephalus (INPH) is considered a potentially treatable neurological disorder by shunt surgery and characterized by a triad of symptoms including gait disturbance, cognitive impairment and urinary dysfunction. Although disorders of white matter are generally viewed as the principal pathological features of INPH, analysis of cortical features are important since the destruction of neural tracts could be associated with cortical structural changing. The aim of the study was to determine whether there was any relationship between gait parameter and structural features of cerebral cortex in INPH patients. Gait parameters were measured as follows: step width, toe in/out angle, coefficient of variation (CV) value of stride length, CV value of stride time. After obtaining individual brain MRI of patients with INPH and hemispheric cortical surfaces were automatically extracted from each MR volume, which reconstructed the inner and outer cortical surface. Then, cortical thickness, surface area, and volume were calculated from the cortical surface. As a result, step width was positively correlated with bilateral postcentral gyrus and left precentral gyrus, and toe in/out was positively correlated with left posterior parietal cortex and left insula. Also, the CV value of stride length showed positive correlation in the right superior frontal sulcus, left insula, and the CV value of stride time showed positive correlation in the right superior frontal sulcus. Unique parameter of cerebral cortical changes, as measured using MRI, might underline impairments in distinct gait parameters in patients with INPH.

• Genomics & Informatics
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• v.19 no.4
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• pp.44.1-44.9
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• 2021

Autism is a complex neurodevelopmental disorder, the prevalence of which has increased drastically in India in recent years. Neuroligin is a type I transmembrane protein that plays a crucial role in synaptogenesis. Alterations in synaptic genes are most commonly implicated in autism and other cognitive disorders. The present study investigated the neuroligin 3 gene in the Indian autistic population by sequencing and in silico pathogenicity prediction of molecular changes. In total, 108 clinically described individuals with autism were included from the North Karnataka region of India, along with 150 age-, sex-, and ethnicity-matched healthy controls. Genomic DNA was extracted from peripheral blood, and exonic regions were sequenced. The functional and structural effects of variants of the neuroligin 3 protein were predicted. One coding sequence variant (a missense variant) and four non-coding variants (two 5'-untranslated region [UTR] variants and two 3'-UTR variants) were recorded. The novel missense variant was found in 25% of the autistic population. The C/C genotype of c.551T>C was significantly more common in autistic children than in controls (p = 0.001), and a significantly increased risk of autism (24.7-fold) was associated with this genotype (p = 0.001). The missense variant showed pathogenic effects and high evolutionary conservation over the functions of the neuroligin 3 protein. In the present study, we reported a novel missense variant, V184A, which causes abnormal neuroligin 3 and was found with high frequency in the Indian autistic population. Therefore, neuroligin is a candidate gene for future molecular investigations and functional analysis in the Indian autistic population.

• Korean Journal of Schizophrenia Research
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• v.24 no.1
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• pp.8-16
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• 2021

Objectives: Although the characteristics of different aggression subtypes provide important information in establishing treatment and prevention strategies in schizophrenia patients, limited information is available about the characteristics of the aggressive subtype in schizophrenia patients in South Korea. The present study was designed to compare the demographic and psychological characteristics across the impulsive and premeditated aggression subtypes in schizophrenia patients in South Korea who had committed a crime. Methods: We enrolled 116 schizophrenia spectrum disorder patients who were admitted to the National Forensic Psychiatric Hospital. Using the criminal and interview records, the study subjects were divided into 83 impulsive and 33 premeditated aggression groups. The subjects' demographic and psychological characteristics were summarized and compared across aggression subtypes. Results: Compared to the premeditated aggression group, the impulsive aggression group had a higher intelligent quotient and a lower rate of physical and sexual abuse experience. Conclusion: To our knowledge, this is the first study to describe the characteristics of aggression subtypes in schizophrenia patients in South Korea who had committed a crime. Our results suggest that different treatment and prevention strategies should be considered for each aggression subtype.

• BMB Reports
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• v.56 no.3
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• The Journal of Korean Obstetrics and Gynecology
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• v.36 no.2
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• pp.20-35
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• 2023

Objectives: The purpose of this study is to review clinical studies and investigate the efficacy and safety of oriental medicine on memory in menopausal women. Methods: 'menopause', 'memory', 'oriental medicine' were searched on 4 online databases (Cochrane Library, Pubmed, CNKI, OASIS). Randomized controlled trials (RCTs) that evaluated menopausal memory with oriental medicine treatment were included. The methodological quality of each RCT was assessed by using Cochrane risk of bias tool. Results: 8 RCTs were selected among 1067 articles. The overall risk of bias was evaluated as uncertain. 5 studies showed that oriental medicine alone was significant effective, but 1 long-term study with the same oriental medicine did not sustain the effect, and 2 studied were not statistically significant. Conclusions: Oriental medicine can be an effective option for improving memory in menopausal women. but considering the small number and quality of studies, inconsistent and insufficient evidence, further well-designed studies are needed to confirm the efficacy and safety of this treatment.

• Journal of Korean Academy of Nursing
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• v.53 no.4
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• pp.371-384
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• 2023

Purpose: With an increase in the aging population, the number of patients with degenerative spinal diseases undergoing surgery has risen, as has the incidence of postoperative delirium. This study aimed to investigate the risk factors affecting postoperative delirium in older adults who had undergone spine surgery and to identify the associated biomarkers. Methods: This study is a prospective study. Data of 100 patients aged ≥ 70 years who underwent spinal surgery were analyzed. Demographic data, medical history, clinical characteristics, cognitive function, depression symptoms, functional status, frailty, and nutritional status were investigated to identify the risk factors for delirium. The Confusion Assessment Method, Delirium Rating Scale-R-98, and Nursing Delirium Scale were also used for diagnosing delirium. To discover the biomarkers, urine extracellular vesicles (EVs) were analyzed for tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light, and glial fibrillary acidic protein using digital immunoassay technology. Results: Nine patients were excluded, and data obtained from the remaining 91 were analyzed. Among them, 18 (19.8%) developed delirium. Differences were observed between participants with and without delirium in the contexts of a history of mental disorder and use of benzodiazepines (p = .005 and p = .026, respectively). Tau and UCH-L1-concentrations of urine EVs-were comparatively higher in participants with severe delirium than that in participants without delirium (p = .002 and p = .001, respectively). Conclusion: These findings can assist clinicians in accurately identifying the risk factors before surgery, classifying high-risk patients, and predicting and detecting delirium in older patients. Moreover, urine EV analysis revealed that postoperative delirium following spinal surgery is most likely associated with brain damage.