• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.27-35
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• 2012

Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

• Journal of Life Science
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• v.22 no.9
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• pp.1231-1236
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• 2012

Exercise leads to the release of certain neurotransmitters in the brain that alleviate pain, both physical and mental. The purpose of this study was to investigate effects of combined exercise on body composition, blood lipids, and brain-derived neurotrophic factor (BDNF) in overweight and obese adolescents. The subjects of this study were 18 boys who were divided into a combined exercise group (EG: n=9) and a control group (CG: n=9). The combined exercise program required exercise 50-60 minutes per day, three times a week, for 12 weeks. The results of the comparative analysis are as follows: The between-group comparison of the difference in the means before and after the intervention revealed a significant decrease in the EG compared with the CG: weight (p<0.01), BMI (p<0.05), %fat (p<0.05), fat mass (p<0.01). The %LBM of the EG showed a more significant increase (p<0.05) compared with the CG. The TC, LDL-C, and BDNF were not different between the EG and the CG. However, the TC and the LDL-C were decreased more in the EG than in the CG. The BDNF was increased more in the EG than in the CG. In conclusion, the combined exercise improved body composition but did not affect serum lipids or the BDNF.

• Journal of Life Science
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• v.28 no.12
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• pp.1536-1544
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• 2018

Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

• Journal of Life Science
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• v.17 no.11
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• pp.1464-1471
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• 2007

Diabetes mellitus is a chronic metabolic disorder, leading to many complications including cognitive deficit. Regular exercise has often been recommended as a therapeutic maneuver to the diabetic patients for the prevention of secondary complications. In the present study, the effects of treadmill exercise on memory and brain-derived neurotrophic factor (BDNF) in the hippocampus of streptozotocin (STZ)-induced diabetic rats were investigated. Male SD rats, aged 6 weeks, were randomly assigned to the following three groups: control group(n=8), STZ-induced diabetic group(n=8), and STZ-induced diabetes and exercise group(n=8). Diabetes was induced by a single injection of STZ (50 mg/kg body weight). Treadmill running was conducted with duration and frequency of 30 minutes and 5 times per week, respectively, for 8 weeks. Memories were tested in the Morris water maze. Western blotting was performed to detect BDNF expression in the hippocampus. In this study, we found that compared to the control group, the STZ-induced diabetes group had a significantly impaired cognitive performance along with suppressed BDNF expression in the hippocampus and the exercise group had a higher cognitive function in diabetic rats. Therefore, the current findings of the study show that a treadmill running exercise can improve diabetes-induced impairment of cognitive function. And the improved cognitive function appears to be related to an alleviation in diabetes-induced BDNF expression in hippocampus.

• Journal of Korean Biological Nursing Science
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• v.4 no.1
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• pp.101-112
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• 2002

Peripheral nerve injury results in plastic changes in the dorsal ganglia (DRG) and spinal cord, and is often complicated with neuropathic pain. The mechanisms underlying these changes are not known, but these changes seem to be most likely related to the neurotrophic factors. This study investigated the effects of mechanical peripheral nerve injury on expression of brain-derived neurotrophic factor(BDNF) in the DRG and spinal cord in rats. 1) Bennett model and Chung model groups showed significantly increased percentage of small, medium and large BDNF-immunoreactive neurons in the ipsilateral $L_4$ DRG compared with those in the contralateral side at 1 and 2 weeks of the injury. 2) In the ipsilateral $L_5$ DRG of the Chung model, percentage of medium and large BDNF-immunoreactive neurons increased significantly at 1 week, whereas that of large BDNF-immunoreactive neurons decreased at 2 week when compared with those in the contralateral side. The intensity of immunoreactivity of each neuron was lower in the ipsilateral than in the contralateral DRG. 3) In the spinal cord, the Bennett and Chung model groups showed a markedly increased BDNF-immunoreactivity in axonal fibers of both superficial and deeper laminae. The present study demonstrates that peripheral nerve injury in neuropathic models altered the BDNF expression in the DRG and spinal cord. This may suggest important roles of BDNF in sensory abnormalities after nerve injury and in protecting the large-sized neurons in the damaged DRG.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.679-688
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• 2018

Autism spectrum disorders (ASDs) are neurodevelopmental disorders that share behavioral features, the results of numerous studies have suggested that the underlying causes of ASDs are multifactorial. Behavioral and/or neurobiological analyses of ASDs have been performed extensively using a valid model of prenatal exposure to valproic acid (VPA). Abnormal synapse formation resulting from altered neurite outgrowth in neural progenitor cells (NPCs) during embryonic brain development has been observed in both the VPA model and ASD subjects. Although several mechanisms have been suggested, the actual mechanism underlying enhanced neurite outgrowth remains unclear. In this study, we found that VPA enhanced the expression of brain-derived neurotrophic factor (BDNF), particularly mature BDNF (mBDNF), through dual mechanisms. VPA increased the mRNA and protein expression of BDNF by suppressing the nuclear expression of methyl-CpG-binding protein 2 (MeCP2), which is a transcriptional repressor of BDNF. In addition, VPA promoted the expression and activity of the tissue plasminogen activator (tPA), which induces BDNF maturation through proteolytic cleavage. Trichostatin A and sodium butyrate also enhanced tPA activity, but tPA activity was not induced by valpromide, which is a VPA analog that does not induce histone acetylation, indicating that histone acetylation activity was required for tPA regulation. VPA-mediated regulation of BDNF, MeCP2, and tPA was not observed in astrocytes or neurons. Therefore, these results suggested that VPA-induced mBDNF upregulation was associated with the dysregulation of MeCP2 and tPA in developing cortical NPCs.

• Journal of Microbiology and Biotechnology
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• v.9 no.3
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• pp.323-327
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• 1999

It was shown that brain-derived neurotrophic factors (BDNFs) secreted from human neuroblastoma cells can significantly improve the growth of the neurites of PC12 nerve cells. The addition of purified BDNFs elongated the neurites of PC 12 nerve cells two to three times more than the case where the addition was not made. The perfusion rate strongly affected the change of the size of human neuroblastoma cells because the cell size decreased as the perfusion rate increased. This could also influence the productivity of BDNF from the cells. It is also important to note that the BDNF production was decreased when the cell size was reduced. BDNF production rate also decreased at a fast perfusion rate in a smaller cell size. At the relatively fast perfusion rate of 18 ml/h, the ratio of apoptotic to necrotic cells dramatically decreased, which possibly caused the decrease of BDNF production. It has been proven that the secretion of BDNF from human neuroblastoma cells was a partially growth-related process by yielding 6.2$\times l0^{-8}/g$ of BDNF/cell/h of growth related parameter and $0.48{\times}l0^{-9}/g$ of BDNF/cell/h of nongrowth-related parameter in a growth kinetic model. In addition, it was also found that the perfusion rate played a very important role in controlling the cell death mechanism.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.308-316
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• 2006

Objectives Despite considerable advances in technique, experience and skill, the precise place of surgery in the treatment of facial nerve injury remains uncertain. We designed a facial nerve crush injury model in rats and evaluated the recovery of crushed nerve which is the most common injury type of facial nerve using adenovirus vector mediated in vivo gene transfer of Brain derived neurotrophic factor(BDNF). Materials and methods In 48 Sprague Dawley rats, we made a facial nerve crush injury model to main trunk before the furcation, and injected a $10^{11}$pfu adenoviral BDNF in experimental group(BDNF adenoviral injection group; ad-BDNF) and $3{\mu}l$ saline in control group(Saline injection group; saline). After a period of regeneration from 10 to 40 days, nerve regeneration was evaluated with functioinal test (vibrissae and ocular movement), electrophysiologic study(threshold, peak voltage, conduction velocity) and histomorphometric study of axon density. Results Vibrissae and ocular movement, threshold and conduction velocity improved as time elapse in both group, however axon density was increased significantly only in experimental group. Functional test in 10 days and 20 days showed no difference between experimental group and control group. Vibrissae movement, threshold, conduction velocity and axon density in 30 days revealed that the regeneration in quality of experimental group was significantly superior to that of control group. Conclusion In general, there is tendency for nerve regeneration in experimental group (BDNF-adenovirus injection group) during 40 days, functional recovery was detected successfully after facial nerve crush in 30 days postoperatively.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.3
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• pp.199-218
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• 2005

Purpose of Study: Peripheral nerve regeneration depends on neurotrophism of distal nerve stump, recovery potential of neuron, supporting cell like Schwann cell and neurotrophic factors such as BDNF. Peripheral nerve regeneration can be enhanced by the conduit which connects the both sides of transected nerve. The conduit maintains the effects of neurotrophism and BDNF produced by Schwann cells which can be made by gene therapy. In this study, we tried to enhance the peripheral nerve regeneration by using calcium phosphate coated porous conduit and BDNF-Adenovirus infected Schwann cells in sciatic nerve of rats. Materials and Methods: Microporous filter which permits the tissue fluid essential for nerve regeneration and does not permit infiltration of fibroblasts, was made into 2mm diameter and 17mm length conduit. Then it was coated with calcium phosphate to improve the Schwann cell adhesion and survival. The coated filter was evaluated by SEM examination and MTT assay. For effective allogenic Schwann cell culture, dorsal root ganglia of 1-day old rat were extracted and treated with enzyme and antimitotic Ara-C. Human BDNF cDNA was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into adenovirus shuttle vector pAACCMVpARS in which E1 was deleted. We infected the BDNF-Ad into 293 human mammary kidney cell-line and obtained the virus plaque 2 days later. RT-PCR was performed to evaluate the secretion of BDNF in infected Schwann cells. To determine the most optimal m.o.i of BDNF-Ad, we infected the Schwann cells with LacZ adenovirus in 1, 20, 50, 75, 100, 250 m.o.i for 2 hours and stained with ${\beta}$-galactosidase. Rats(n=24) weighing around 300g were used. Total 14mm sciatic nerve defect was made and connected with calcium phosphate coated conduits. Schwann cells$(1{\times}10^6)$ or BDNF-Ad infected Schwann cells$(1{\times}10^6)$ were injected in conduit and only media(MEM) was injected in control group. Twelve weeks after surgery, degree of nerve regeneration was evaluated with gait analysis, electrophysiologic measurements and histomorphometric analysis. Results: 1. Microporous Millipore filter was effective conduit which permitted the adhesion of Schwann cells and inhibited the adhesion of fibroblast. We could enhance the Schwann cell adhesion and survival by coating Millipore filter with calcium phosphate. 2. Schwann cell culture technique using repeated treatment of Ara-C and GDNF was established. The mean number of Schwann cells obtained 1 and 2 weeks after the culture were $1.54{\pm}4.0{\times}10^6$ and $9.66{\pm}9.6{\times}10^6$. 3. The mRNA of BDNF in BDNF-Ad infected Schwann cells was detected using RT-PCR. In Schwann cell $0.69\;{\mu}g/{\mu}l$ of DNA was detected and in BDNF-Adenovirus transfected Schwann cell $0.795\;{\mu}g/{\mu}l$ of DNA was detected. The most effective infection concentration was determined by LacZ Adenovirus and 75 m.o.i was found the most optimal. Conclusion: BDNF-Ad transfected Schwann cells successfully regenerated the 14mm nerve gap which was connected with calcium phosphate coated Millipore filter. The BDNF-Ad group showed better results compared with Schwann cells only group and control group in aspect to sciatic function index, electrophysiologic measurements and histomorphometric analysis.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1443-1446
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• 2018

In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed $TNF-{\alpha}$ expression and $NF-{\kappa}B$ activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited $NF-{\kappa}B$ activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting $NF-{\kappa}B$ activation.