• Journal of Life Science
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• v.18 no.6
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• pp.796-803
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• 2008

Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.298-304
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• 2016

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

• The Journal of Pediatrics of Korean Medicine
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• v.25 no.1
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• pp.40-48
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• 2011

Objectives: The purpose of this study is to evaluate the effect of Gonjadaesungchimjoongbang on spatial learning abilities and memories in ischemic brain injury. Methods: Rats were separated into three groups; (1) Normal, (2) Saline medication after ischemic brain injuries (control), (3) Gonjadaesungchimjoongbang medication after ischemic brain injuries (experiment). Ischemic brain injuries was induced by MCA occlusion and reperfusion. Morris water maze test was conducted for spatial learning and memory tests. Then, the change of BDNF in the hippocampus($7^{th}$, $14^{th}$ day) was examined by immunohistoche- mistry. Results: In Morris water maze test, spatial learning abilities and memory functioning were considerably increased in the experiment group as oppose to control group on $7^{th}$ and $14^{th}$ day(p<0.01). Moreover, immunohistochemistric response of BDNF in the hippocampus indicated that the more increased immune reaction was found in the experiment group as oppose to the control group on $7^{th}$ and $14^{th}$ day. Conclusions: Gonjadaesungchimjoongbang can improve the learning abilities and memories in ischemic brain injury.

• Journal of Magnetics
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• v.17 no.3
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• pp.225-228
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• 2012

Muscle contusion usually results from a direct blunt impact and is frequently associated with contact sports. Muscle contusion results from microscopic muscle fiber and capillary disruption causing a microhemorrhage dissecting torn fibers and remaining viable muscle fibers. Recent studies concluded that some physical methods, including pulsed ultrasound (PU) and pulsed electromagnetic field (PEMF) treatment, accelerate and facilitate wound healing, improve scar quality and have beneficial effects on muscle and tendon healing. However, there are few studies on the effects of the early use of physical methods, such as PU and PEMF, on the expression of neurotrophic factors. The objective of this study was to investigate the effects of the early application of PU and PEMF, measured through the expression of BDNF in the muscles (gastrocnemius) and spinal cords of rats after skeletal muscle contusion. In the spinal cords and muscles, there was a significant increase of BDNF expression in the PEMF and PU groups, a greater increase was found in the PEMF group than in the PU group. In conclusion, PEMF is a useful therapeutic method that improves muscle healing after muscle contusion.

• Psychiatry investigation
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• v.15 no.11
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• pp.1094-1097
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• 2018

Objective Patients with acute coronary syndrome (ACS) are at an increased risk of suicide. It is well known that epigenetic mechanisms may explain the pathophysiology of suicidal behavior including suicidal ideation (SI), but no study has explored these mechanisms in ACS populations. Methods In total, 969 patients were initially recruited within 2 weeks of the acute coronary event and, 711 patients were successfully followed up 1 year after ACS. SI was evaluated using the relevant items on the Montgomery-${\AA}sberg$ Depression Rating Scale and covariates potentially affecting SI were estimated. Results Brain-derived neurotrophic factor (BDNF) hypermethylation was associated with SI in both the acute and chronic phases of ACS, although the association was not statistically significant in the acute phase after applying Bonferroni's correction. Conclusion These results suggested that BDNF hypermethylation may have played a role in an epigenetic predisposition for SI in ACS patients, particularly during the chronic phase.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.310-316
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• 2020

Kyung-Ok-Go (KOK) is a traditional prescription used for debilitating natural aging and post-illness debilitation. KOK has been used in a variety of ways because it strengthens immunity, prevents illness, and helps recovery in case of illness. In particular, recent research has revealed that KOK helps improve memory and cognition. Therefore, in this study, we investigated whether KOK was effective in improving memory decline and depression-state observed during menopause. In the present study, we employed ovariectomized mouse as an animal model for measuring menopausal syndrome. The administration of KOK for 8 weeks, the object recognition memory and working memory were improved in novel object recognition test and Y-maze test. And in the forced swimming test, the immobility time were decreased. Additionally, the expression level of mature brain derived neurotropic factor (mBDNF) was increased by KOK administration in ovariectomized mouse hippocampus. These results suggested that KOK could improve cognitive decline and depression during menopausal period, and it might be come from enhancing expression level of mBDNF in hippocampus.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.261-270
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• 2022

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus's effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 µL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 µL/rat) suppressed orexin's effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.65-76
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• 2024

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.361-370
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• 2017

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.51-72
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• 2009

Objectives : This study was designed to evaluate the effects of Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture on pain reduction and nerve regeneration after crush injury in rat sciatic nerve. Methods : Animal model was produced through crush injury of right sciatic nerve and they were divided into four groups; Group I: no treatment control group; Group II: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san); Group III: experimental group treated with Jungsongouhyul pharmacopuncture; Group IV: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture. For the assessment of pain, this study was observed the paw withdrawal latency(PWL) and immunoreactivity on the substance-P. For the assessment of nerve regeneration, the sciatic functional index(SFI) and immunoreactivity on the BDNF were measured. Results : 1. In the assessment of pain, the PWL of experimental groups was significantly higher than control group and group IV was significantly higher than other groups at the all days. 2. In immunohistochemical response of substance-P, as time passes, the immunoreactivity of all groups were decreased gradully. Especially, group IV had the lowest immunoreactivity. 3. In the assessment of SFI, the SFI of experimental groups were significantly higher than control group. 4. In immunohistochemical response of BDNF, the BDNF immunoreactivity of all groups was significantly higher than control group and especially, group IV had the highest immunoreactivity at the 14 days after injury. 5. H & E stain was used on the liver and kidney to investigate toxic effect of Jungsongouhyul pharmacopuncture and Ohyaksungi-san(Wuyaoshungi-san) on on 21 days after injury. However there were no any toxic effects both control group and experimental groups. Conclusions : On the basis of these results, we propose that Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture were related to pain reduction and motor nerve recovery, also decreased substance-P expression and increased BDNF expression after crush injury of sciatic nerve, especially these two treatments could be more effective when they were combined simultaneously.