• Nutrition Research and Practice
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• v.13 no.4
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• pp.286-294
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• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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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.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.71-77
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• 2019

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by $A{\beta}_{1-42}$ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin ($100{\mu}g/kg/day$), the cognitive impairment of mice induced by $A{\beta}_{1-42}$ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and $A{\beta}_{1-42}$ accumulation in hippocampus. $A{\beta}_{1-42}$ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

• Journal of Oriental Neuropsychiatry
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• v.32 no.1
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• pp.25-37
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• 2021

Objectives: Depression is a mood disorder showing low energy, loss of interest, anhedonia, and anxiety. It affects a patients' daily life. This disease is considered a social problem because the patient may commit suicide in extreme cases. JSB is composed of 12 Korean medicinal herbs. It has been prescribed to patients with depression. The objective of this study is to investigate anti-depressive effects of JSB on restraint stress-induced depression in a mouse model. Methods: Depression was induced by restraint stress. Mice were orally administered JSB at 10, 20, or 40 mg/kg for 14 days. Forced swimming test (FST) and open field test (OFT) were performed. Brain-derived neurotrophic factor (BDNF) mRNA level was measured by real time-PCR. Plasma levels of corticosterone and serotonin were measured by ELISA. Blood levels of AST and ALS were measured using a biochemical analyzer. Results: JSB treatment significantly reduced the immobility time in FST. BDNF mRNA level was increased by JSB treatment in the hippocampi of mice. Although the expression of TNF-α was also increased by JSB, such increase was not statistically significant. The increase of corticosterone level in plasma induced by restraint stress was significantly down-regulated by JSB. JSB reduced blood level of AST, but not ALT. Conclusions: JSB has a potential to manage depression, setting a foundation for clinical application of Korean medicine with safety.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.1
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• pp.18-22
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• 2022

To investigate effects of cognitive function improvement whether against Taegeuk ginseng on scopolamine-induced memory impairment in rats. All experiments were conducted in three groups: the control group (CTR), the scopolamine 0.4mg/kg (SCP), and the scopolamine (SCP+T) treated with Taegeuk ginseng 100 mg/kg. Taegeuk ginseng 100 mg/kg daily was orally administered for one month and treated with scopolamine was only for 7 consecutive days on the Morris water maze task. 3 weeks after oral administration of Taegeuk ginseng, subjects were performed the Morris water maze test for 8 days and then the open-field exploration test which to assessed for cognitive function improvement. After behavioral testing, subjects were sacrificed and microdissected brains for neurochemical analysis. In the cognitive-behavioral test, long-term administration of Taegeuk ginseng improved spatial navigation learning task compared with the impeded by scopolamine treatment. In neurochemistry, the expression of the synaptic marker PSD95 (postsynaptic density protein 95) was increased in the hippocampus compared to the scopolamine group. Also, brain-derived neurotrophic factor (BDNF) expression was significantly increased in the taegeuk ginseng administration group. These data suggested that long-term administration of taegeuk ginseng might improve cognitive-behavioral functions on hippocampal related spatial learning memory, and it was correlated with neurotropic and synaptic reinforcement. In conclusion, treatment with taegeuk ginseng may positive outcome on learning and memory deficit disorders.

• 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).

• Korean Journal of Medicinal Crop Science
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• v.19 no.6
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• pp.456-463
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• 2011

The present study examined the effects of Korean white ginseng (WG, Panax ginseng C. A. Meyer) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered with saline or WG (WG 100 or 300 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of WG on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing immunohistochemistries on choline acetyltransferase (ChAT), acetylcholinesterase (AchE), cAMP responsive element binding protein (CREB) and brain derived neurotrophic factor (BDNF). The rats treated with TMT injection (control group) showed impaired learning and memory of the tasks, but the rats treated with TMT injection and WG administration produced significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd and 4th days compared to that of the control group. In the retention test, the WG 100 and WG 300 groups showed significantly increased crossing number around the platform compared to that of the control group (p < 0.001). Consistently with the behavioral data, result of immunohistochemistry analysis showed that WG 100 mg/kg significantly alleviated the loss of BDNF-ir neurons in the hippocampus compared to that of the control group (p < 0.01). Also, treatment with WG has a trend to be increased the cholinergic neurons in the hippocampal CA1 and CA3 areas as compared to that of the control group. These results suggest that WG may be useful for improving the cognitive function via regulation of neurotrophic activity.

• ALGAE
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• v.31 no.1
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• pp.73-84
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• 2016

Marine organisms are frequently used to be harmful and have lower side effects than synthetic drugs. The cognitive improving efficacy of gamma aminobutyric acid-enriched fermented Saccharina japonica (FSJ) on the memory deficient rats, which were induced by trimethyltin chloride (TMT), was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), cAMP response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) immunohistochemistry. The neurite outgrowth of Neuro2a cells was assessed in order to examine the underlying mechanisms of the memory enhancing effects of FSJ. Treatment with FSJ tended to shorten the latency to find the platform in the acquisition test of the Morris water maze at the second and fourth day compared to the control group. In the probe trial, the FSJ treated group increased time spent in the target quadrant, compared to that of the control group. Consistent with the behavioral data, these treatments recovered the loss of ChAT, CREB, and BDNF immunepositive neurons in the hippocampus produced by TMT. Treatment with FSJ markedly stimulated neurite outgrowth of the Neuro2a cells as compared to that of the controls. These findings demonstrate that FSJ may be useful for improving the cognitive function via regulation of neurotrophic marker enzyme activity.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.2
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• pp.117-127
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• 2002

Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.3
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• pp.191-198
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• 2017

Background: For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. Method: In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. Results: The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). Conclusion: Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits.