• Korean Journal of Biological Psychiatry
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• v.19 no.2
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• pp.91-98
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• 2012

Objectives : The aim of this study was to examine the effects of brain-derived neurotrophic factor (BDNF) genetic polymorphism and job stress on the severity of alcohol drinking. It was hypothesized that individuals with the Met/Met BDNF genotype would be more vulnerable than those carrying the Val allele. Methods : Participants were 133 healthy Korean adults (mean age $28.2{\pm}1.1$). Job stress and the severity index of drinking were investigated through self-reported questionnaires. BDNF (rs6265) gene was genotyped. Results : There was no significant association between job stress and the severity of alcohol drinking. Although the severity of alcohol drinking was not associated with BDNF genetic polymorphism, there was a significant difference in men according to genotype and job stress. Men with homozygous BDNF Met allele were more severe in alcohol drinking when job stress was high, less severe in alcohol drinking when job stress was low than those carrying the Val allele (F = 4.47, p = 0.038). Also higher level of job stress was correlated with higher severity of alcohol drinking in men homozygous for BDNF Met allele (rs = 0.620, p = 0.005). Conclusions : These findings suggest the possibility that Met allele could have differential susceptibility, with men homozygous for BDNF Met allele being more susceptible to both more adverse and less adverse environmental influences.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.462-469
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• 2013

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.

• Journal of Acupuncture Research
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• v.35 no.1
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• pp.28-36
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• 2018

Background: This study investigated the effects of acupuncture at Sobu (HT8) and Haenggan (LR2) on scopolamine-induced, cognitively impaired rats. Methods: Scopolamine-treated Sprague-Dawley rats were divided into 6 groups; normal, control, HT8, LR2, HT8 + LR2 and sham group. Cognitive impairment was induced by scopolamine, in control, and then in HT8, LR2, HT8 + LR2 and sham groups. Acupuncture treatment was performed at HT8, LR2, HT8 + LR2, and a random acupoint, respectively, every other day for 2 weeks. After each treatment, behavior change was observed and the rats were sacrificed. The change in brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase activity was evaluated by polymerase chain reaction. Results: Latency time to target in Morris Water-Maze test for the HT8 + LR2 group showed a significant decrease compared with control (p<0.05). Target crossing times and time zone ratios in Morris Water-Maze test for HT8 + LR2 group showed a significant increase compared with control (p<0.01). In the Y-Maze test the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase, in the HT8 + LR2 group, showed a significantly increased level compared with control (p<0.05). Neural activity of acetylcholine esterase in HT8 + LR2 group showed a significant decrease compared with the control group (p<0.01), choline acetyltransferase activity in the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Conclusion: Acupuncture at HT8 + LR2 restored scopolamine-induced cognitive impairment, suggesting acupuncture could be an alternative to improve cognitive function.

• Applied Microscopy
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• v.48 no.3
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• pp.55-61
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• 2018

The synaptic vesicle is a specialized structure in presynaptic terminals that stores various neurotransmitters. The actin filament has been proposed for playing an important role in mobilizing synaptic vesicles. To understand the role of actin filament on synaptic vesicle pooling, we characterized synaptic vesicles and actin filament after treatment of brain-derived neurotrophic factor (BDNF) or Latrunculin A on primary cultured neuron from rat embryo hippocampus. Western blots revealed that BDNF treatment increased the expression of synapsin I protein, but Latrunculin A treatment decreased the synapsin I protein expression. The increased expression of synapsin I after BDNF disappeared by the treatment of Latrunculin A. Three-dimensional (3D) tomography of synapse showed that more synaptic vesicles localized near the active zone and total number of synaptic vesicles increased after treatment of BDNF. But the number of synaptic vesicle was 2.5-fold reduced in presynaptic terminals and the loss of filamentous network was observed after Latrunculin A application. The treatment of Latruculin A after preincubation of BDNF group showed that synaptic vesicle number was similar to that of control group, but filamentous structures were not restored. These data suggest that the actin filament plays a significant role in synaptic vesicles pooling in presynaptic terminals.

• The Korea Journal of Herbology
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• v.35 no.5
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• pp.33-39
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• 2020

Objectives : Increasing evidence supports the biological and pharmacological activities of essential oils on the central nervous system such as pain, anxiety, attention, arousal, relaxation, sedation and learning and memory. The purpose of present work is to investigate the protective effect and molecular mechanism of cypress essential oil (CEO) against scopolamine (SCO)-induced cognitive impairments in C57BL/6 mice. Methods : A series of behavior tests such as Morris water maze, passive avoidance, and fear conditioning tests were conducted to monitor learning and memory functions. Immunoblotting and RT-PCR were also performed in the hippocampal tissue to determine the underlying mechanism of CEO. Results : SCO induced cognitive impairments as assessed by decreased step-through latency in passive avoidance test, relatively low freezing time in fear conditioning test, and increased time spent to find the hidden platform in Morris water maze test. Conversely, CEO inhalation significantly reversed the SCO-induced cognitive impairments in C57BL/6 mice comparable to control levels. To elucidate the molecular mechanisms of memory enhancing effect of CEO we have examined the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. CEO effectively elevated the protein as well as mRNA expression of BDNF via activation of cAMP response element binding protein (CREB). Conclusions : Our findings suggest that CEO inhalation effectively restored the SCO-impaired cognitive functions in C56BL/6 mice. This learning and memory enhancing effect of CEO was partly mediated by up-regulation of BDNF via activation of CREB.

• 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 Life Science
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• v.27 no.8
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• pp.879-887
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• 2017

It is well established that brain-derived neurotrophic factor (BDNF) is expressed not only in the brain but also in skeletal muscle, and is required for normal neuromuscular system function. Histone deacetylases (HDACs) and insulin-like growth factor-I (IGF-I) are potent regulators of skeletal muscle myogenesis and muscle gene expression, but the mechanisms of HDAC and IGF-I in skeletal muscle-derived BDNF expression have not been examined. In this study, we examined the effect of IGF-I and suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, on BDNF induction. Proliferating or differentiating C2C12 skeletal muscle cells were treated with increasing concentrations (0-50 ng/ml) of IGF-I in the absence or presence of $5{\mu}M$ SAHA for various time periods (3-24 hr). Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent decrease in BDNF mRNA expression. However, inhibition of HDAC led to a significant increase in the expression of BDNF mRNA levels. In addition, immunocytochemistry revealed high BDNF protein levels in undifferentiated C2C12 skeletal muscle cells, whether untreated, IGF-I-treated, or exposed to SAHA. These results represent the first evidence that IGF-I can suppress the mRNA and protein expression of BDNF; conversely, SAHA attenuates the effects of IGF-I. Consequently, SAHA upregulates BDNF expression in C2C12 skeletal muscle cells.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• 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.

• The Journal of Korean Physical Therapy
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• v.19 no.4
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• pp.33-41
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• 2007

Purpose: To investigate environmental enrichment and nerve stimulation follows in application times with the change of BDNF & Trk-B receptor in the motor cortex and spinal cord. Methods: Experimental groups were divided into the five groups. Group I: normal control group, Group II: experiment control group, Group III: sciatic never electrical stimulation after MCAO, Group IV: application of only environmental enrichment after MCAO, Group V: never electrical stimulation with environmental enrichment after MCAO. Histologic observation and coronal sections were processed individually in goat polyclonal antibody phosphorylated BDNF and rabbit polyclonal antibody Trk-B receptor. Results: In immunohistochemistric response of BDNF and Trk-B, group II were showed that lower response effect at postischemic 1 days, 3 days, and 7 days. Group V were showed that increase response effect at postischemic 3 days, 7 days and 14 days. Specially showed that the most response effect at postischemic 14 days. In neurobehavioral assessment, group V were significantly difference from other groups on between-subject effects. Conclusion: The above results suggest that combined environmental enrichment with peripheral nerve electrical stimulation in focal ischemic brain injury were more improved that the change of BDNF & Trk-B receptor expression than non treatment.