• Journal of Life Science
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• v.16 no.3 s.76
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• pp.464-471
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• 2006

Peripheral nerve injuries are a commonly encountered clinical problem and often result in severe functional deficits. In the present study, the effects of treadmill exercise on neurotrophin expressions and functional recovery following sciatic crushed nerve injury were investigated. Animals were randomly assigned into four groups: the sciatic nerve injury group, the sciatic nerve injury and 3-day-exercise, the sciatic nerve injury and 7-days-exercise, and the sciatic nerve injury and 14-days-exercise groups. Sciatic nerve injury was caused by crushing the right sciatic nerve for 30 s using a surgical clip. A the light-exercise was applied to each of the exercise group over the respective number of days. In the present results, we identified enhanced axonal re-growth in the distal stump of the sciatic nerve 3-14 days after crush injury with treadmill training. Dorsal root ganglion (DRG) neuron when cultured from animals with nerve injury and treadmill training showed more enhanced neurite outgrowth than that of sedentary animals. Nerve growth factor (NGF) protein levels in low-intensity treadmill training group were highly induced in the injured sciatic nerves 3, 7 and 14 days after injury compared with sedentary group, and brain-derived neurotrophin factor (BDNF) protein levels in treadmill exercise group were highly induced in the injured sciatic nerve 3 days after injury compared with sedentary group. Then, treadmill exercise increased neurotrophic factors induced in the regenerating nerves. We further demonstrate that motor functional recovery after sciatic nerve injury was promoted by treadmill exercise. Thus, the present data provide a new evidence that treadmill exercise enhanced neurotrophins expression and axonal regeneration after sciatic nerve injury in rats.

• Journal of Life Science
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• v.22 no.5
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• pp.569-574
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• 2012

This study was conducted to investigate the effect of exercise on oxidative stress, nerve growth, and hepatocyte growth factors in obese children. After 12 weeks of aerobic exercise training, the aforementioned parameters before and after the training were compared. As a result, the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were shown to be lower in the OT than in the NT before and after the training, respectively ($p$ <0.05). The NGF was shown to have increased in both groups after the training ($p$ <0.05). The hepatocyte growth factor (HGF) was shown to be higher in the OT than in the NT before the training ($p$ <0.05), with no difference found afterwards. The malondialdehyde (MDA), ox-LDL, and 8-OHdG (Oxo-2'-deoxyguanosine) were shown to be higher in the OT than in the NT ($p$ <0.05). For ox-LDL, a difference was found between before and after the training ($p$ <0.05). The results of this study showed that obesity induced oxidative stress and caused the abnormalities of nerve and HGF secretion in obese children, and that the 12 weeks of aerobic exercise increased NGF levels, thereby promoting the development of neurogenesis in children.

• The Journal of Korean Physical Therapy
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• v.17 no.4
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• pp.589-600
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• 2005

The purposes of this study is to discuss and analyze the effect on the recovery from cut in sciatic nerve. This study used 9 weeks male rats of Sprague-Dawley family. Rat in groups 4 were treated with pulsed therapeutic ultrasound for 3 minutes. 3 times weekly at 3MHz respectively (intensity; $0.2W/cm^2,\;0.5W/Cm^2,\;10W/cm^2$); rat in group 1 received placebo ultrasound. In addition, changes of serum aspartate amino-transferase(AST) and creatine phosphokinase(CPK) levels were also demonstrated with diameter of individual muscle fasciculate and number of muscle fiber in each of three types of muscles located in gastrocnemius, soles. The results of comparing the changes in groups are as follows; 1. We found out that hypertrophic epineurium was present in sciatic nerve injured ultrasound treatment of groups. 2. In the gastrocnemius morphological investigation of the group I (control group), severe muscle atrophy were observed at the 7th days of the sciatic nerve injury. however, muscle atrophy of the group IV ($1.0W/cm^2$) were slightly recovered at the 14th days after treatment ultrasound. At the 28th days, muscular fibers were formed in polygon and were significantly recovered. 3. C-fos immunoreactive of the group II ($0.2W/cm^2$), III ($0.5W/cm^2$) were remarkably increased at the 1th day after treatment of ultrasound. Group IV were markedly deceased. 4. Brain-Derived Neurotrophic Factor(BDNF) immunoreactive of the group II, III were increased after 7 days of the sciatic nerve injury. Group IV were markedly increased from 14th days to 28th days after treatment of ultrasound. 5. A significant increase of serum AST levels were demonstrated in control group. However, serum AST levels of massage groups were significantly decreased compared to that of control group in followed order ; ($0.2W/cm^2<0.5W/cm^2<1.0W/cm^2$). 6. A significant increase of serum CK levels were demonstrated in control of group. However, serum CK levels of massage groups were significantly decreased compared to that of control group in followed order ; ($0.2W/cm^2<0.5W/cm^2<1.0W/cm^2$). The above results suggest that ultrasound treatment after peripheral nerve injury might reduce noxious stimuli, facilitate nerve recovery and effective in the functional improvement delaying muscle atrophy or degeneration.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.379-386
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• 2012

The purpose of this study was to evaluate whether berberine (BER) administration could attenuate depression- and anxiety-like behaviors and increase corticotrophin-releasing factor (CRF) and tyrosine hydroxylase (TH) expression following chronic morphine withdrawal in rats. Male rats were exposed to chronic, intermittent, escalating morphine (10~50 mg/kg) for 10 days. After the last morphine injection, depression- and anxiety-like beahvior associated with morphine discontinuation persisted for at least three days during withdrawal without any change in ambulatory activity. Daily BER administration significantly decreased immobility in the forced swimming test and increased open-arm exploration in the elevated plus maze test. BER administration also significantly blocked the increase in hypothalamic CRF expression and TH expression in the locus coeruleus (LC) and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression. Taken together, these findings demonstrated that BER administration significantly reduced morphine withdrawal-associated behaviors following discontinuation of repeated morphine administration in rats, possibly through modulation of hypothalamic CRF and the central noradrenergic system. BER may be a useful agent for treating or alleviating complex withdrawal symptoms and preventing morphine use relapses.

• 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.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.285-297
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• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.3-19
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• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• Korean Journal of Exercise Nutrition
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• v.16 no.2
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• pp.73-84
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• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.