• Fisheries and Aquatic Sciences
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• v.25 no.8
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• pp.450-461
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• 2022

A randomized, double-blind, and placebo-controlled clinical study was used to determine the cognitive functions related to working memory (WM) and antioxidant properties of fermented Laminaria japonica (FLJ) on healthy volunteers. Eighty participants were divided into a placebo group (n = 40) and FLJ group (n = 40) that received FLJ (1.5 g/day) for 6 weeks. Memory-related blood indices (brain-derived neurotrophic factor, BDNF; angiotensin-converting enzyme; human growth hormone, HGH; insulin-like growth factor-1, IGF-1) and antioxidant function-related indices (catalase, CAT; malondialdehyde, MDA; 8-oxo-2'-deoxyguanosine, 8-oxo-dG; thiobarbituric acid reactive substances, TBARS) were determined before and after the trial. In addition, standardized cognitive tests were conducted using the Cambridge Neuropsychological Test Automated Batteries. Furthermore, the Korean Wechsler Adult Intelligence Scale (K-WAIS)-IV, and the Korean version of the Montreal Cognitive Assessment (MoCA-K) were used to assess the pre and post intake changes on WM-related properties. According to the results, FLJ significantly increased the level of CAT, BDNF, HGH, and IGF-1. FLJ reduced the level of TBARS, MDA, and 8-oxo-dG in serum. Furthermore, FLJ improved physical activities related to cognitive functions such as K-WAIS-IV, MoCA-K, Paired Associates Learning, and Spatial Working Memory compared to the placebo group. Our results suggest that FLJ is a potential candidate to develop functional materials reflecting its capability to induce antioxidant mechanisms together with WM-related indices.

• Journal of Life Science
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• v.19 no.4
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• pp.449-456
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• 2009

Murine Neuro-2a (N2a) cells have been widely used for the investigation of neuronal differentiation, trophic interaction and neurotoxic effects of various compounds and their associated mechanisms. N2a cells have many genomic variations such as gains or losses in DNA copy number, similar to other neuroblastoma cells, and no systematic or high-resolution studies of their genome-wide chromosomal aberrations have been reported. Presently, we conducted a systematic genome-wide determination of chromosomal aberrations in N2a cells using a high-throughput, oligonucleotide array-based comparative genomic hybridization (oaCGH) technique. A hidden Markov Model was employed to assign each genomic oligonucleotide to a DNA copy number state: double loss, single loss, normal, gain, double gain and amplification. Unlike most neuroblastoma cells, Mycn amplification was not observed in N2a cells. In addition, these cells showed gain only in the neuron-derived neurotrophic factor (NF), while other neurotrophic factors such as glial line-derived NF and brain-derived NF presented normal copy numbers. Chromosomes 4, 8, 10, 11 and 15 displayed more than 1000 aberrational oligonucleotides, while chromosomes 3, 17, 18 and 19 displayed less than 20. The largest region of gain was located on chromosome 8 and its size was no less than 26.7 Mb (Chr8:8427841-35162415), while chromosome 4 had the longest region of single deletion, with a size of 15.1 Mb (Chr4:73265785-88374165).

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1585-1591
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• 2013

The purpose of this study is to examine how to relate with hypothalamus protein BDNF and mRNA leptin expression, and test the effect of exercise training upon anti-obesity in high-fat induced obese rats. Weight and plasma TC of the high-fat diet group (HF) significantly reduced in comparison to those in the high-fat diet and training group (HF-T), high-fat diet and normal diet group (HF-ND), and high-fat diet, training, and normal diet group (HF-ND+T) (P<0.05). Plasm TG of the HF group significantly decreased in comparison to the HF-ND+T group (P< 0.05). The plasma leptin level significantly reduced in the HF-T group in comparison to the HF group, in the HF-ND group compared to the HF-T group, and the HF-ND+T group in comparison to the HF-ND group (P<0.05, respectively). All groups were significantly increased in hypothalamus BDNF protein expression in comparison to the HF group. In hypothalamus leptin mRNA expression, the HF-T and HF-ND groups reduced, but the HF-NF+T group increased in comparison to the HF group. This result suggests that it shows the effect of exercise training upon anti-obesity in high-fat diet induced obese rats and the combined exercise and/or normal diet may affect the optimal obesity improvement and prevention in appetite and weight control.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2001.12a
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• pp.22-37
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• 2001

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.

• Fisheries and Aquatic Sciences
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• v.26 no.1
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• pp.24-34
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• 2023

Reactive oxygen species (ROS) at high concentrations induce oxidative stress, an imbalanced redox state that is a prevalent cause of neurodegenerative disorders. This study aimed to investigate the protective effect of Capsosiphon fulvescens (CF) extract on oxidative stress-induced impairment of cognitive function in models of neurodegenerative diseases. CF was extracted with subcritical water and several solvents and H₂O₂ (0.25 mM) or aluminum chloride (AlCl₃; 25 µM) as an inducer of ROS was treated in PC12 neuronal cells and zebrafish larvae. All statistical analyses were performed using one-way analysis of variance and Dunnett's test using GraphPad Prism. H₂O₂ and AlCl₃ were found to significantly induce ROS production in PC12 neuronal cells and zebrafish larvae. In addition, they strongly affected intracellular Ca²⁺ levels, antioxidant enzyme activity, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling, acetylcholinesterase (AChE) activity, and hallmarks of Alzheimer's disease. However, treatment of H₂O₂-induced PC12 cells or AlCl₃-induced zebrafish larvae with CF subcritical water extract at 90℃ and CF water extract effectively regulated excessive ROS production, intracellular Ca²⁺ levels, and mRNA expression of superoxide dismutase, glutathione peroxide, glycogen synthase kinase-3 beta, β-amyloid, tau, AChE, BDNF, and TrkB. Our study suggested that CF extracts can be a potential source of nutraceuticals that can improve the impairment of cognitive function and synaptic plasticity by regulating ROS generation in neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.393-403
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• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.228-235
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• 2010

This study was performed to investigate the memory enhancing effect of Poria cocos Wolf (Hoelen cum radix) against scopolamine-induced amnesia in Sprague-Dawley (SD) rats. To induce amnesia, scopolamine (0.75 mg/kg) was intraperitonically injected into SD rats 30 min before starting behavior tests. We have conducted Morris water-maze and Y-maze tests to monitor learning and memory functions. Poria cocos effectively reversed scopolamine-induced memory impairment in SD rats which was represented by an improvement of mean escape latency in water-maze test and spontaneous alterations in Y-maze test. To elucidate possible molecule mechanism, we have measured mRNA as well as protein expression of acetylcholine esterase (AchE), choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), and brain-derived neurotrophic factor (BDNF) using RT-PCR and Western blot analysis, respectively. Poria cocos increased mRNA levels of ChAT and mAchR in rat hippocampus compared with those in the scopolamine-injected amnesic group. In addition, protein expression of ChAT and BDNF was also elevated by Poria cocos intake. Furthermore, as an upstrem regulator, the activation of cAMP response element-binding protein (CREB) was assessed by immunohistochemistry. In this immunohistochemical analysis, the phosphorylation of CREB (p-CREB) was reduced by scopolamine injection, which was restored back to control levels by administration of Poria cocos. These results suggest that Poria cocos may improve memory and cognitive deficit in amnesia and have therapeutic potentials through up-regulation of ChAT, mAchR, and BDNF, which seemed to be mediated by activation of CREB.

• Journal of Ginseng Research
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• v.40 no.1
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• pp.55-61
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• 2016

Background: A number of neurological and neurodegenerative diseases share impaired cognition as a common symptom. Therefore, the development of clinically applicable therapies to enhance cognition has yielded significant interest. Previously, we have shown that activation of lysophosphatidic acid receptors (LPARs) via gintonin application potentiates synaptic transmission by the blockade of $K^+$ channels in the mature hippocampus. However, whether gintonin may exert any beneficial impact directly on cognition at the neural circuitry level and the behavioral level has not been investigated. Methods: In the current study, we took advantage of gintonin, a novel LPAR agonist, to investigate the effect of gintonin-mediated LPAR activation on cognitive performances. Hippocampus-dependent fear memory test, synaptic plasticity in the hippocampal brain slices, and quantitative analysis on synaptic plasticity-related proteins were used. Results: Daily oral administration of gintonin for 1 wk significantly improved fear memory retention in the contextual fear-conditioning test in mice.We also found that oral administration of gintonin for 1 wk increased the expression of learning and memory-related proteins such as phosphorylated cyclic adenosine monophosphate-response element binding (CREB) protein and brain-derived neurotrophic factor (BDNF). In addition, prolonged gintonin administration enhanced long-term potentiation in the hippocampus. Conclusion: Our observations suggest that the systemic gintonin administration could successfully improve contextual memory formation at the molecular and synaptic levels as well as the behavioral level. Therefore, oral administration of gintonin may serve as an effective noninvasive, nonsurgical method of enhancing cognitive functions.

• Journal of Ginseng Research
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• v.28 no.2
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• pp.94-103
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• 2004

Korean red ginseng is known to have anti-stress and memory enhancing effects. Recent studies suggested that stress-induced inhibition of adult neurogenesis in hippocampus may contribute, in part, to decreased negative feedback inhibition of HPA axis. In order to elucidate the mechanism of Korean red ginseng in anti-stress and memory enhancing effects, we observed the effects of repeated treatment of Korean red ginseng total saponin (GTS, 50 mg/kg, i.p.) in response to repeated unpredictable stress for 10 days. Male Sprague-Dawley rats (230 - 260 g) received with either GTS (50 mg/kg, i.p.) or vehicle (1 ml/kg, i.p.) 1 h before stress for 10 days. Rats were injected with bromodeoxyuridine (BrdU, 50 mg/kg, i.p.) 16-18 he after last stress procedure, and were sacrificed 2 hr later by perfusion. Immunohistochemistry of BrdU was done to measure proliferation of neural progenitor cells in hippocampus, which was used as an index of neurogenesis. Repeated GTS treatment for 10 days increased neurogenesis in subgranular zone area of dentate gyrus (SGZ), but not hilus, compared with vehicle-treated rats. Repeated unpredictable stress did not affect the neurogenesis compared with controls, while repeated GTS treatment increased neurogenesis in SGZ in repeated unpredictable stress-exposed group. BDNF mRNA was also measured in subregions of hippocampus by in situ hybridization. BDNF mRNA expression in CA3 and CA1 pyramidal cell layer was increased by repeated GTS treatment but not in dentate granule cell layer. Repeated unpredictable stresses significantly decreased BDNF mRNA expression in all subregions of hippocampus, but repeated GTS treatment did not prevent stress-induced BDNF mRNA downregulation. Given that repeated GTS treatment increased proliferation of neural progenitor cells in repeated unpredictable stress-exposed rats in the presence of decreased BDNF mRNA expression in dentate granule cell layer, it raise the possibility that BDNF may not playa significant role in GTS-mediated increase of neurogenesis in adult rat hippocampus. Also, these results suggest that repeated GTS treatment increased neurogenesis of SGZ and BDNF mRNA expression, which may account for memory enhancing effect of Korean red ginseng. In addition, repeated GTS treatment appears not to have anti-stress effects in terms of neurotrophin, but GTS-mediated increase of neurogenesis in hippocampus may contribute to increase negative feedback inhibition of HPA axis.

• 한국체육학회지인문사회과학편
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• v.54 no.1
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• pp.553-566
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• 2015

This study was performed to identify the effects of different intensities of regular aerobic exercise on erythropoietin (EPO) and BDNF levels, and cognitive function and working memory in middle-aged women. Women aged 40 to 60 years residing in G-gu, Y-si, Gyeonggi-do were divided into 3 groups: control group, moderate-intensity aerobic exercise group and high-intensity aerobic exercise. All groups were asked to exercise at the given intensities, twice a week for a total of 12 weeks. Blood samples were collected from participants on week 0 (before exercising), week 6 and week 12, and then cognitive function and working memory tests were followed to measure erythropoietin (EPO) and BDNF levels, cognitive function and working memory. Repeated measures ANOVA, univariate analysis and follow-up test were performed on all data to compare the group, period and interaction through a SPSS. As a result, a significant difference over time was observed in EPO, BDNF, cognitive function and working memory; therefore, a follow-up one-way ANOVA analysis was performed on each group. As a result of analysis, a significant increase in erythrocyte, hematocrit, BDNF level and working memory was observed in moderate-intensity aerobic exercise group while erythrocyte and working memory were significantly increased inhigh-intensity aerobic exercise group. When comparing the results between the groups, the level of hematocrit was shown to be significantly higher in both moderate-and high-intensity aerobic group than the control group and also the higher level of hemoglobin was observed in both moderate-and high-intensity aerobic group comparing to control group. Considering the results of this study, therefore, a 12-week long aerobic exercise at moderate to high intensity positively affected EPO and BDNF levels, cognitive function and working memory in middle-aged women.