• Journal of Ginseng Research
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• 제33권2호
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• pp.132-138
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• 2009

Previous studies suggest that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. In this study, whether red ginseng (RG) could attenuate memory impairment was investigated through a passive-avoidance and object recognition memory test, as well as the suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) in adult mice treated with a relatively low-dose exposure to gamma radiation (0.5 or 2.0 Gy). RG was administered intraperitonially at a dosage of 50 mg/kg of body weight, at 36 and 12 h pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg! kg of body weight/day for seven days before autopsy. In the passive-avoidance and object recognition memory test, the mice that were trained for one day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells was significantly decreased. RG treatment prior to irradiation attenuated the memory defect and blocked apoptotic death as well as a decrease in the Ki-67- and DCX-positive cells. RG may attenuate memory defect in a relatively low-dose exposure to radiation in adult mice, possibly by inhibiting the detrimental effect of irradiation on hippocampal neurogenesis.

• Journal of Korean Medical Science
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• 제33권46호
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• pp.289.1-289.10
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• 2018

Background: Cerebral microbleeds (CMBs) are associated with cerebrovascular risk factors and cognitive dysfunction among patients with Parkinson's disease (PD). However, whether CMBs themselves are associated with PD is to be elucidated. Methods: We analyzed the presence of CMBs using 3-Tesla brain magnetic resonance imaging in non-demented patients with PD and in age-, sex-, and hypertension-matched control subjects. PD patients were classified according to their motor subtypes: tremor-dominant, intermediate, and postural instability-gait disturbance (PIGD). Other cerebrovascular risk factors and small vessel disease (SVD) burdens were also evaluated. Results: Two-hundred and five patients with PD and 205 control subjects were included. The prevalence of CMBs was higher in PD patients than in controls (16.1% vs. 8.8%; odds ratio [OR], 2.126; P = 0.019); CMBs in the lobar area showed a significant difference between PD patients and controls (11.7% vs. 5.9%; OR, 2.234; P = 0.032). According to the motor subtype, CMBs in those with PIGD type showed significant difference from controls with respect to the overall brain area (21.1% vs. 8.9%; OR, 2.759; P = 0.010) and lobar area (14.6% vs. 4.9%; OR, 3.336; P = 0.016). Among PD patients, those with CMBs had higher age and more evidence of SVDs than those without CMBs. Conclusion: We found that CMBs are more frequent in PD patients than in controls, especially in those with the PIGD subtype and CMBs on the lobar area. Further study investigating the pathogenetic significance of CMBs is required.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.422-433
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• 2018

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

• 생물치료정신의학
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• 제24권3호
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• pp.218-229
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• 2018

Objectives : Antipsychotic-induced hyperprolactinemia causes physical symptoms, such as amenorrhea, galactorrhea, gynecomastia, sexual dysfunction, and bone density loss, as well as psychiatric symptoms, such as depression and cognitive impairments. This study aimed to clarify the associations among hyperprolactinemia caused by antipsychotics in patients with schizophrenia, psychiatric pathology, and psychosocial factors. Methods : Ninety-nine patients with schizophrenia in the psychiatry department of a university hospital were registered between 2015 and 2017. All participants were assessed using structured questionnaires to elucidate psychopathology, social function, quality of life, and hyperprolactinemia-related side effects. The standard levels for hyperprolactinemia were 24ng/mL for women and 20ng/mL for men. Results : The average prolactin levels were $73.45{\pm}49.37ng/mL$ in patients with hyperprolactinemia and $9.16{\pm}6.42ng/mL$ in those without hyperprolactinemia. The average prolactin level in women was significantly higher than that in men(p=0.04). Risperidone was most commonly administered in patients with hyperprolactinemia(58.1%, p<0.01), while aripiprazole was most commonly administered in those without hyperprolactinemia(44.7%, p<0.01). Patients with hyperprolactinemia had significantly higher Positive and Negative Syndrome Scale(p=0.03) and Patient Health Questionnaire-9(p=0.05) scores and had significantly lower Social and Occupational Functioning Assessment Scale(p=0.04) and Strauss-Carpenter Levels of Functioning Scale(p=0.03) scores than patients without hyperprolactinemia. There were no significant differences in side effects or quality of life between the two groups. Conclusion : These findings demonstrate that hyperprolactinemia confers negative effects on depression and social function, but does not directly affect the quality of life. These results suggest that patients with schizophrenia who take antipsychotics that increase prolactin or cause side effects of hyperprolactinemia need to be assessed and receive interventions for depression.

• Journal of mucopolysaccharidosis and rare diseases
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• 제5권1호
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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.

• 수면정신생리
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• 제28권1호
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• pp.18-26
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• 2021

Sleep is essential to brain function and mental health. Insomnia and obstructive sleep apnea (OSA) are the two most common sleep disorders, and are major public health concerns. Proton magnetic resonance spectroscopy (¹H-MRS) is a non-invasive method of quantifying neurometabolite concentrations. Therefore, ¹H-MRS studies on individuals with sleep disorders may enhance our understanding of the pathophysiology of these disorders. In this article, we reviewed ¹H-MRS studies in insomnia and OSA that reported changes in neurometabolite concentrations. Previous studies have consistently reported insomnia-related reductions in γ-aminobutyric acid (GABA) levels in the frontal and occipital regions, which suggest that changes in GABA are important to the etiology of insomnia. These results may support the hyperarousal theory that insomnia is associated with increased cognitive and physiological arousal. In addition, the severity of insomnia was associated with low glutamate and glutamine levels. Previous studies of OSA have consistently reported reduced N-acetylaspartate (NAA) levels in the frontal, parieto-occipital, and temporal regions. In addition, OSA was associated with increased myo-inositol levels. These results may provide evidence that intermittent hypoxia induced by OSA may result in neuronal damage in the brain, which can be related to neurocognitive dysfunction in patients with OSA. The current review summarizes findings related to neurochemical changes in insomnia and OSA. Future well-designed studies using ¹H-MRS have the potential to enhance our understanding of the pathophysiology of sleep disorders including insomnia and OSA.

• 대한의용생체공학회:의공학회지
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• 제42권6호
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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.

• BMB Reports
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• 제56권3호
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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.

• 농업과학연구
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• 제49권1호
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• pp.137-149
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• 2022

We investigated the effects of Cirsium japonicum var. maackii (CJM) against oxidative stress-induced C6 glial cells and cognitive impairment in mice. To evaluate the anti-oxidative effect of the extract and fractions from CJM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and nitric oxide (NO) assays were conducted in H₂O₂-treated C6 glial cells. Furthermore, we identified the protective mechanisms of CJM with a scopolamine-treated mice model. The results revealed that H₂O₂ decreased the cell viability in C6 glial cells, indicating that H₂O₂ induced oxidative stress in glial cells. However, CJM fractions significantly increased cell viability in H₂O₂-treated C6 glial cells, which suggested that CJM protected against oxidative stress. CJM extract and fractions also reduced ROS and NO production, which were increased by H₂O₂ in C6 glial cells. In particular, the EtOAc fraction from CJM (EACJM) effectively protected against oxidative stress by increasing the cell viability and decreasing ROS and NO. Therefore, we carried out further in vivo experiments with EACJM. Scopolamine caused increases of ROS, thiobarbituric acid reactive substances (TBARS), and NO production. However, EACJM effectively alleviated ROS, TBARS, and NO levels compared to scopolamine-injected mice. In addition, EACJM up-regulated protein expressions of superoxide dismutase and glutathione peroxidase, indicating that EACJM enhanced the antioxidative system. Our results demonstrated that CJM had protective effects against oxidative stress in glial cells and memory dysfunction in mice. Based on these results, we propose that CJM could be a potential AD preventive and therapeutic agent.

• 대한한방부인과학회지
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• 제36권2호
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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.