• Journal of Korean Biological Nursing Science
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• v.21 no.3
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• pp.217-223
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• 2019

Purpose: Caffeine is the most widely consumed psychostimulant of the methylxanthine class. Among adolescents, high-dose of caffeine consumption has increased rapidly over the last few decades due to the introduction of energy drinks. However, little is known about the time-dependent effect of high doses of caffeine consumption in adolescents. The present study aims to examine the short- and long-term influence of high-dose caffeine on behavior of adolescence. Methods: The animals were divided into three groups: a "vehicle" group, which was injected with 1 ml of phosphate-buffered saline for 14 days; a "Day 1" group, which was injected with caffeine (30 mg/kg), 2 h before the behavioral tests; and a "Day 14" group, which was infused with caffeine for 14 days. An open-field test, a Y-maze test, and a passive avoidance test were conducted to assess the rats'activity levels, anxiety, and cognitive function. Results: High-dose caffeine had similar effects in short-and long-term treatment groups. It increased the level of locomotor activity and anxiety-like behavior, as evidenced by the increase in the number of movements and incidences of rearing and grooming in the caffeine-treated groups. No significant differences were observed between the groups in the Y-maze test. However, in the passive avoidance test, the escape latency in the caffeine-treated group was decreased significantly, indicating impaired memory acquisition. Conclusion: These results indicate that high-dose caffeine in adolescents may increase locomotor activity and anxiety-like behavior and impair learning and memory, irrespective of the duration of administration. The findings will be valuable for both evidence-based education and clinical practice.

• Neonatal Medicine
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• v.25 no.4
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• pp.178-185
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• 2018

Purpose: We aim to assess the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), Adaptive Behavior (AB) and Social-Emotional (SE) scales at 18 to 24 months of corrected age (CA) to examine their associations with school-age cognitive and behavioral outcomes in children born preterm. Methods: Eighty-eight infants born with a very low birth weight (<1,500 g) or a gestational age of less than 32 weeks who were admitted to the neonatal intensive care unit from 2008 to 2009 were included. Of the 88 children who completed school-age tests at 6 to 8 years of age, 37 were assessed using the Bayley-III, including the AB and SE scales, at 18 to 24 months of CA. Correlation, cross-tabulation, and receiver operating characteristic analyses were performed to assess the longitudinal associations. Results: A significant association was observed between communication scores on the Bayley-III AB scale at 18 to 24 months of CA and the Korean version of the Wechsler Intelligence Scale for Children (K-WISC) full-scale intelligence quotient (FSIQ) at school age (r=0.531). The total behavior problem scores of the Korean version of the Child Behavior Checklist (K-CBCL) at school age were significantly negatively related to the Bayley-III SE and AB scales but not to the cognitive, language, or motor scales. Conclusion: Our findings encourage AB and SE assessments during the toddler stage and have important implications for the early identification of children in need of intervention and the establishment of guidelines for follow-up with high-risk infants.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.85-85
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• 2019

Objective: In this study, the anti-stress effects of extract of Hydrangeae Dulcis Folium (EHDF) or ethalonic extract of Opuntiaficus-indica (EOF) of natural extracts from Jeju Island were investigated. Methods: We performed measurement of whole-body cortisol level and behavioral experiments including the novel tank test (NTT) or the open field test (OFT) to assess stress responses in zebrafish. To induce physical stress, we used the net handling stress (NHS). Fish were treated with EOF or EHDF for 6 min before they were exposed to stress. And then, we sacrificed fish for collecting body fluid from whole-body or conducted behavioural tests, including novel tank test and open field test, were evaluated to observe anxiety-like behaviours and locomotion. We used the cortisol enzyme-linked immunoassay kit to measure the amount of cortisol in each zebrafish sample. Results: The results indicate that increased anxiety-like behaviours in novel tank test and open field test under stress were prevented by treatment with both EOF and EHDF (P < 0.05). Moreover, compared with the unstressed group, which was not treated with NHS, the whole-body cortisol level was significantly increased by treatment with NHS. Compared with the NHS-treated stressed control group, pre-treatment with each EHDF and EOF for 6 min significantly prevented the NHS-increased whole-body cortisol level (P < 0.05). Conclusions: In conclusion these results suggest that both EOF and EHDF pretreatment may prevent stress responses and that its mechanism of action may be related to its positive effects on cortisol release.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.376-386
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• 2022

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.572-584
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• 2022

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.819-829
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• 2022

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABA_A antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABA_A receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.43-48
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• 2015

Objectives : The aim of this study was to investigate the memory enhancing properties of extract of Hoelen Cum Radix (HCR) and its possible mechanism in mice of normal condition. Methods : We evaluated the effects of HCR on cognitive function and memory enhancement in normal mice. Male ICR mice were orally administrated with HCR 100 mg/kg for 7 days and equal volume of saline was administrated to the control group in the same condition. We conducted two behavioral tests which measure the spatial working memory (Y-maze test) and cognitive fear memory (passive avoidance test). We also investigated whether HCR affects the hippocampal neurogenesis in the brain. To assess the effects of HCR on neural progenitor cell differentiation and neurite outgrowth in the early stage of hippocampal neurogenesis, we performed doublecortin (DCX), a direct neurogenesis marker, immunohistochemical analysis in the dentate gyrus (DG) of the mouse hippocampus. Results : HCR significantly enhanced memory and cognitive function as determined by the Y-maze test (p<0.05) and passive avoidance test (p<0.001). Moreover, HCR increased DCX positive cells (p<0.01) and neurite length (p<0.01) compared to the control group. These results indicated that HCR stimulates differentiation of neural progenitor cells and promotes neurite outgrowth in hippocampal DG of the mice. Conclusion : We concluded that HCR shows memory enhancing effects through the stimulation of hippocampal neurogenesis as a consequence of accelerated neuronal differentiation and neurite outgrowth in the DG of the hippocampus after HCR treatment.

• Korean Journal of Veterinary Research
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• v.62 no.3
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• pp.25.1-25.9
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• 2022

Canine cognitive dysfunction syndrome (CDS) is a neurodegenerative disease that causes cognitive and behavioral disorders and reduces the quality of life in dogs and their guardians. This study reviewed the complementary and alternative medicine (CAM) for CDS and compared the diagnosis and therapy of CAM between CDS in canines and dementia in humans. The evaluation tools for the diagnosis of CDS and dementia were similar in the neurological and neuropsychiatric examinations, daily life activity, cognitive tests, and neuroimaging, but the evaluation for dementia was further subdivided. In CAM, pattern identification is a diagnostic method for accurate, personalized treatment, such as herbal medicine. For herbal medicine treatment of cognitive impairment in canines and humans, a similar pattern identification classified as deficiency (Qi, blood, and Yin) and Excess (phlegm, Qi stagnation, and blood stasis) is being used. However, the veterinary clinical basis for verifying the efficacy and safety of CAM therapies for CDS is limited. Therefore, based on CAM evidence in dementia, it is necessary to establish CDS-targeted CAM diagnostic methods and therapeutic techniques considering the anatomical, physiological, and pathological characteristics of dogs.

• Korean Journal of Audiology
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• v.23 no.1
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• pp.1-7
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• 2019

Self-reported difficulties in speech-in-noise (SiN) recognition are common among tinnitus patients. Whereas hearing impairment that usually co-occurs with tinnitus can explain such difficulties, recent studies suggest that tinnitus patients with normal hearing sensitivity still show decreased SiN understanding, indicating that SiN difficulties cannot be solely attributed to changes in hearing sensitivity. In fact, cognitive control, which refers to a variety of top-down processes that human beings use to complete their daily tasks, has been shown to be critical for SiN recognition, as well as the key to understand cognitive inefficiencies caused by tinnitus. In this article, we review studies investigating the association between tinnitus and cognitive control using behavioral and brain imaging assessments, as well as those examining the effect of tinnitus on SiN recognition. In addition, three factors that can affect cognitive control in tinnitus patients, including hearing sensitivity, age, and severity of tinnitus, are discussed to elucidate the association among tinnitus, cognitive control, and SiN recognition. Although a possible central or cognitive involvement has always been postulated in the observed SiN impairments in tinnitus patients, there is as yet no direct evidence to underpin this assumption, as few studies have addressed both SiN performance and cognitive control in one tinnitus cohort. Future studies should aim at incorporating SiN tests with various subjective and objective methods that evaluate cognitive performance to better understand the relationship between SiN difficulties and cognitive control in tinnitus patients.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.402-410
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• 2023

Long-term administration of levodopa (L-DOPA) to patients with Parkinson's disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.