• Biomedical Science Letters
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• v.30 no.1
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• pp.1-9
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• 2024

Although there have been several attempts to use virtual reality (VR) in the treatment of depression, the results have been inconsistent and existing studies have mostly relied on subjective measures to assess the effectiveness of VR in improving depression. The aim of this study was to investigate the effect of nature experience-based VR intervention on depressive symptoms in a young population using both subjective and objective measurements. The study population included 15 participants who had more than 14 identifiers of the Korean Beck Depression Inventory (K-BDI)-II. Participants received three weeks (four times per week) of VR intervention. The effectiveness of VR was assessed through changes in K-BDI-II scores and depression-related blood biomarkers. Nature experience-based VR intervention led to an approximately 50% reduction of K-BDI-II score (before 25.7±7.7 vs. after 12.5±8.3 (P<0.001)). Of these, loss of pleasure and fatigue showed the largest amount of improvement. However, levels of cortisol, brain-derived neurotrophic factor, and interleukin-6 did not differ from those at baseline. The findings of our pilot study suggest that nature experience-based VR can be a useful adjunctive treatment method for improving depressive symptoms in individuals who have difficulty accessing the real outside natural environment.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• Journal of Korean Neurosurgical Society
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• v.44 no.6
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• pp.375-381
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• 2008

Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Applied Microscopy
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• v.39 no.1
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• pp.1-7
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• 2009

Experimental induction of polycystic ovary (PCO) resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins (GTS) in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that therapeutic GTS administration modulates sympathetic nerve activity in rats with PCO. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF mRNA expression in PCO rats compared to control rats, and PCO ovaries were counteracted by GTS administration with significantly lower expression of NGF mRNA compared to EV treated ovaries. However, NGF protein was unaffected in both EV and GTS treated ovaries compared to control rats. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.

• The Journal of the Korea Contents Association
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• v.11 no.4
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• pp.273-282
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• 2011

This study was to investigate the effect of improve forelimb sensorimotor function and neurotrophic factor(GAP-43) expression when differing an application time of tDCS in ischemic brain injury rat model(pre, $1^{st}$, $7^{th}$, $14^{th}$). Focal ischemic brain injury was induced in 80 Sprague-Dawley rats through middle cerebral artery occlusion(MCAO) by 'Longa' method. And then experimental groups were randomly divided into four groups; GroupI: MCAO induction, GroupII: application of tDCS(10 min) after MCAO induction, GroupIII: application of tDCS(20 min) after MCAO induction, GroupIV: application of tDCS(30 min) after MCAO induction. Modified limb placing test and single pellet reaching test were performed to test forelimb sensorimotor function. And the histological examination was also observed through the immunohistochemistric response of GAP-43(growth-associated protein-43) in the cerebral cortex. In modified limb placing test, groupIII(p<0.05) showed significantly improve than the other groups on $14^{th}$). day. In single pellet reaching test, groupIII(p<0.01) and groupIV(p<0.05) significantly improved on $14^{th}$) day. And in immunohistochemistric response of GAP-43, group III showed significantly positive response than the other groups on $14^{th}$ day. These results suggest that the intensity(0.1 mA)/time(20 min) condition of tDCS application has a significant impact on the sensorimotor functional recovery in focal ischemic brain injury rat models.

• 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.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.107-115
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• 2018

Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and $N_{\omega}$-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.

• 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.

• Korean Journal of Food Science and Technology
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• v.53 no.6
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• pp.715-721
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• 2021

Cognitive impairment and Alzheimer's disease are serious social problems associated with the rising elderly population in Korea. 1,2,3,4,6-Penta-O-galloyl-β-ᴅ-glucopyranose (PGG) is a gallotannin isolated from medicinal plants such as Rhus chinensis. This study was performed to evaluate the effect of PGG on biomarkers related to cognitive function in human neuroblastoma SK-N-SH cells. Inhibition of acetylcholinesterase (AChE) activity is considered to be one of the main therapeutic strategies. PGG inhibited AChE activity in the test tube as well as in SK-N-SH cells. In addition, PGG induced protein and mRNA expression of brain-derived neurotrophic factor (BDNF), which is a mammalian neurotrophin that plays major roles in the development, maintenance, repair, and survival of neuronal populations. As one of the underlying molecular mechanisms that induce BDNF expression, PGG induced the activation of Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII)-cAMP response element binding protein (CREB) pathway. In conclusion, PGG may be an useful material for improving cognitive function.