• BMB Reports
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• v.47 no.7
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• pp.369-375
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• 2014

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic bioactive peptide that was first isolated from an ovine hypothalamus in 1989. PACAP belongs to the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily. PACAP is widely distributed in the central and peripheral nervous systems and acts as a neurotransmitter, neuromodulator, and neurotrophic factor via three major receptors (PAC1, VPAC1, and VPAC2). Recent studies have shown a neuroprotective role of PACAP using in vitro and in vivo models. In this review, we briefly summarize the current findings on the neurotrophic and neuroprotective effects of PACAP in different brain injury models, such as cerebral ischemia, Parkinson's disease (PD), and Alzheimer's disease (AD). This review will provide information for the future development of therapeutic strategies in treatment of these neurodegenerative diseases.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.39-50
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• 2009

Objective : The aim of this study was to evaluate the effects of Aconiti ciliare tuber on the descending pain and the recovery of locomotor function that results from sciatic crushed nerve injury in rats. Method : In order to assess the effects of the aqueous extract of Aconiti ciliare tuber on the recovery rate of locomotor function, we investigated the walking track analysis, and for the effects on the pain control we investigated brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression in the sciatic nerve and on the expressions of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region resulting from the sciatic crushed nerve injury in rats. Result : Treatment with Aconiti ciliare tuber significantly enhanced the SFIvalue, enhanced BDNF expression, decreased iNOS expression, and suppressed c-Fos expression. The present results showed that Aconiti ciliare tuber facilitated functional recovery following sciatic crushed nerve injury in rats. The recovery mechanisms of SFI by Aconiti ciliare tuber might be ascribed to the increase of BDNF expression for nerve regeneration and reinnervation and to the suppression of iNOS expression for inhibiting nerve inflammation. Conclusion : In this process it has been shown that Aconiti ciliare tuber can be used for pain control and functional recovery from peripheral nerve injury.

• Natural Product Sciences
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• v.19 no.4
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• pp.324-328
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• 2013

Soy (Glycine max, family Leguminosae) contains isoflavones and saponins as main constituents. In our preliminary study, soybean ethanol extract (SE) ameliorated scopolamine-induced memory impairment in mice in the passive avoidance task. Therefore, to confirm its ameliorating effect for memory impairments, we measured its effect in scopolamine-induced memory-impaired mice in Morris water maze task. SE significantly prevented scopolamine-induced memory impairment in the Morris water maze task. SE also increased the swimming time within quadrant section of the platform on the day after the final training session test. SE protected the reduction of brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation in the hippocampi of scopolamine-treated mice. However, SE did not inhibit acetylcholinesterase. To understand the possible role of soysaponins in memory impairments, we prepared soyasaponins-rich (butanol) fraction of soybean (SRF) and investigated its protective effect against in the passive avoidance and Morris water maze tasks. SRF ameliorated scopolamine-induced memory impairment in mice. The memory impairment-ameliorating effect of SRF was more effective than that of SE. Based on these findings, soybean may improve memory impairment by regulating CREB phosphorylation and BDNF expression.

• Anxiety and mood
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• v.11 no.2
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• pp.129-135
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• 2015

Objective : Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of several neuropsychiatric disorders. However, there are few studies on BDNF of panic disorder. In this study, we investigated plasma BDNF levels in patients with panic disorder, and evaluated whether there are associations between clinical characteristics of panic disorder and plasma BDNF levels. Methods : We included 110 patients with panic disorder and 110 health controls in the current study. Plasma BDNF levels were measured by the enzyme-linked immunosorbent assay (ELISA). Plasma BDNF level differences were evaluated according to the clinical characteristics, such as duration of illness, recent stressful life event, agoraphobia, and insomnia. Results : The mean plasma BDNF levels of patients with panic disorder were significantly lower, as compared with those of controls (192.50 pg/mL vs. 693.75 pg/mL, t=8.838, p<0.001). The mean plasma BDNF levels of patients who had recent stressful life events were significantly higher, as compared with those who did not ($269.79{\pm}358.96pg/mL$ vs. $136.94{\pm}187.06pg/mL$, t=-2.525, p=0.013). Conclusion : These results suggested that BDNF plays a potential role in the pathophysiology of panic disorder.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.467-473
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• 2014

The purpose of this study is to investigate the memory enhancing effect and underlying molecular mechanism of arabinoxylan (AX), a major component of dietary fiber in wheat against scopolamine (SCO)-induced amnesia in Sprague-Dawley (SD) rats. Diverse behavior tests including Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. SCO significantly decreased the spontaneous alterations in Y-maze test and step-through latency in passive avoidance test, whereas increased time spent to find the hidden platform in Morris water maze test compared with the sham control group. In contrast, oral administration of AX (25 mg/kg and 50 mg/kg) effectively reversed the SCO-induced cognitive impairments in SD rats. Furthermore, AX treatment up-regulated the expression of brain-derived neurotrophic factor (BDNF) in the cortex and hippocampus via promoting activation of cAMP response element binding protein (CREB). Therefore, our findings suggest that AX can improve SCO-induced learning and memory impairment possibly through activation of CREB and up-regulation of BDNF levels, thereby exhibiting a cognition-enhancing potential.

• Toxicological Research
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• v.27 no.2
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• pp.103-110
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• 2011

Lipotoxicity involves pathological alterations to cells and tissues in response to elevated fat levels in blood. Furthermore, this process can disturb both cellular homeostasis and viability. In the current study, the authors show that neural progenitor cells (NPCs) are vulnerable to high levels of palmitic acid (PA) a saturated fatty acid. PA was found to cause cell death associated with elevated reactive oxygen species (ROS) levels, and to reduce NPCs proliferation. To evaluate the lipotoxicity of PA in adult NPCs in the hippocampus, male C57BL/6 mice were divided into two groups and maintained on either a normal diet (ND) or PA-rich high fat diet (HFD) for 2 weeks. Interestingly, short-term PA-rich HFD feeding reduced the survival of newly generated cells in the hippocampal dentate gyrus and hippocampal brain-derived neurotrophic factor levels. These findings suggest PA has a potent lipotoxicity in NPCs and that a PA-rich HFD disrupts hippocampal neurogenesis.

• Journal of Korean Neurosurgical Society
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• v.60 no.4
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• pp.391-396
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• 2017

Objective : To investigate the neuroprotective effects of Ginkgolide B (GB) against ischemic stroke-induced injury in vivo and in vitro, and further explore the possible mechanisms concerned. Methods : Transient middle cerebral artery occlusion (tMCAO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells were used to explore the neuroprotective effects of GB. The expression of brain-derived neurotrophic factor (BDNF) was detected via Western blot and qRT-PCR. Results : GB treatment (4 mg/kg, i. p., bid) significantly reduced neurological deficits, water content, and cerebral infarct volume in tMCAO mice. GB also significantly increased Bcl-2/Bax ratio, reduced the expression of caspase-3, and protected against OGD/R-induced neuronal apoptosis. Meanwhile, GB caused the up-regulation of BDNF protein in vivo and in vitro. Conclusion : Our data suggest that GB might protect the brain against ischemic insult partly via modulating BDNF expression.

• 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.

• BMB Reports
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• v.53 no.12
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• pp.646-651
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• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.

• Korean Journal of Biological Psychiatry
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• v.30 no.1
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• pp.1-6
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• 2023

Many psychiatric disorders are associated with brain functional dysfunctions and neuronal degeneration. According to the research so far, enhanced brain plasticity reduces neurodegeneration and recovers neuronal damage. Brain-derived neurotrophic factor (BDNF) is one of the most extensively studied neurotrophins in the mammalian brain that plays major roles in neuronal survival, development, growth, and maintenance of neurons in brain circuits related to emotion and cognitive function. Also, BDNF plays an important role in brain plasticity, influencing dendritic spines in the hippocampus neurogenesis. Changes in neurogenesis and dendritic density can improve psychiatric symptoms and cognitive functions. BDNF has potent effects on brain plasticity through biochemical mechanisms, cellular signal pathways, and epigenetic changes. There are pharmacological and non-pharmacological interventions to increase the expression of BDNF and enhance brain plasticity. Non-pharmacological interventions such as physical exercise, nutritional change, environmental enrichment, and neuromodulation have biological mechanisms that increase the expression of BDNF and brain plasticity. Non-pharmacological interventions are cost-effective and safe ways to improve psychiatric symptoms.