• Journal of Korean Neurosurgical Society
• /
• 제66권5호
• /
• pp.511-524
• /
• 2023

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

• 한방재활의학과학회지
• /
• 제21권2호
• /
• pp.143-158
• /
• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problem and often result in severe functional deficits. The aim of this study is to evaluate the effects of aqueous extract of Achyranthes japonica(AJ) on functional recovery in sciatic nerve after crushed sciatic nerve injury. Methods : In the present study, the animals in the AJ-treated groups received the aqueous extract of AJ at the respective doses orally for 13 consecutive days. In order to assess the effects of the aqueous extract of AJ on function recovery in crushed sciatic nerve injury, sciatic functional index(SFI) was performed. c-Fos expression in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG), and neurofilament, and the expressions of brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF) following crushed sciatic nerve injury in rats were investigated. For this, immunohistochemistry and western blot were performed. Results : In the present study, crushed sciatic nerve injury showed characteristic gait changes showing decrease of SFI value and treatment with the aqueous extract of AJ significantly enhanced the SFI value. Neurofilament expression in the sciatic nerve was decreased by crushed sciatic nerve injury and treatment with the AJ increased neurofilament expression. The expressions of BDNF and NGF in the sciatic nerve were increased following crushed sciatic nerve injury and treatment with the AJ significantly controlled the sciatic nerve injury-induced increment of BDNF and NGF expressions. c-Fos expressions in the PVN and vIPAG were increased following crushed sciatic nerve injury and treatment with the AJ significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions. Conclusions : These results suggest that AJ treatment after crushed sciatic nerve injury is effective in the functional recovery by enhancing axonal regeneration and suppressing of pain.

• Molecules and Cells
• /
• 제21권2호
• /
• pp.237-243
• /
• 2006

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.

• 생약학회지
• /
• 제50권4호
• /
• pp.253-259
• /
• 2019

Chaenomeles speciose Nakai (CSP) or Chaenomeles sinensis Koehne (CSS) (Rosaceae) has been used, traditionally, to treat muscle problems and gastric dampness in eastern Asia countries. Therefore, many studies have focused on investigating its active compounds and effects on muscle pain, arthritis and gastro-intestinal diseases. Recently, several studies reported that CSS extract degrade amyloid plaques and enhance synaptic acetylcholine level in vivo and in vitro. Although these two Chaenomeles species are used without differences, CSP is reported to contains more phenolic compounds which are known to enhance memory. Therefore, in this study, we investigated the memory ameliorating effects of CSP by employing the passive avoidance test, Y-maze task and novel object recognition test. CSP (30 or 100 mg/kg) ameliorated the declined memory induced by scopolamine injection and enhanced the brain-derived neurotrophic factor (BDNF) levels along with post synaptic density protein 95 (PSD 95) levels at the hippocampus of the scopolamine-injected mouse brain. These results suggested that CSP alleviates the cognition declines caused by cholinergic blockade via enhancing BDNF levels and PSD 95, and that it would enhance memory formation and be useful for treating memory declines.

• Animal cells and systems
• /
• 제16권3호
• /
• pp.190-197
• /
• 2012

Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권4호
• /
• pp.281-296
• /
• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• 생물정신의학
• /
• 제12권2호
• /
• pp.189-195
• /
• 2005

Objects:Some studies have suggested that brain-derived neurotrophic factor(BDNF), one of the most important neurotrophins, is involved in pathophysiology of depression and suicide. This study was performed to determine whether there is an abnormality in plasma BDNF concentration in suicidal attempters. Methods:The subjects were 71 suicidal attempters who visited emergency rooms in multi-medical centers. All subjects had been interviewed by using Structured Clinical Interview for DSM-IV(SCID), Hamilton Depression Rating Scale(HDRS), Young Mania Rating Scale(YMRS), and Positive And Negative Syndrome Scale(PANSS). The severity of the suicidal behavior was measured by Lethality of Suicide Attempt Rating Scale(LSARS) and Risk-Rescue Rating(RRR) system. Seventy-one age, sex, and diagnosis matched non-suicidal psychiatric patients who were consecutively admitted to a psychiatric ward during the same period recruited as psychiatric controls. They were drug-naive or drug-free at least more than 2 months. In addition, 80 healthy controls were randomly selected as normal controls. Plasma BDNF level was measured by the enzyme linked immunosorbent assay(ELISA) methods. Results:In overall F-test, differences of the plasma BDNF levels among the groups were statistically significant(F=20.226, p<0.001). In the multiple comparisons(Scheffe), while mean levels of plasma BDNF between normal controls and non-suicidal psychiatric patients were similar(p=0.984), the BDNF levels of suicidal attempters were lower than those of other two groups(p<0.001). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal attempters. Conclusion:These results suggest that reduction of plasma BDNF level is related to suicidal behavior and BDNF level may be a biological marker of suicidal behavior.

• 생명과학회지
• /
• 제17권11호
• /
• pp.1464-1471
• /
• 2007

당뇨병은 만성적 대사질환으로 말초뿐만 아니라 중추신경계에서도 다양한 합병증을 유발시키는 것으로 알려져 있다. 특히, 당뇨환자는 인지기능의 손상으로 인해 치매 유병율이 높은 것으로 보고되고 있다. 규칙적인 운동은 당뇨병의 이차 합병증을 예방하기 위한 치료적 방법으로 흔히 권장된다. 이에 본 연구는 당뇨흰쥐를 대상으로 트레드밀 운동이 기억력과 해마 BDNF 발현에 미치는 효과를 조사하였다. SD계열 흰쥐를 실험동물로 하여 STZ (50 mg/kg) 투여로 유발시킨 당뇨흰쥐를 8주간 주 5회 30분씩 트레드밀에서 달리도록 하였다. 운동프로그램 종료 후, Morris water maze로 기억력을 측정하고, 해마조직을 적출하여 Western으로 brain-derived neurotrophic factor (BDNF) 발현을 정량화하였다. 본 연구결과 8주간의 당뇨는 선행연구과 유사하게 기억력 손상과 함께 해마 조직의 BDNF 발현을 유의하게 감소시키는 것으로 나타났다. 하지만 트레드밀 운동은 당뇨흰쥐에서 기억력과 해마 BDNF 발현을 유의하게 향상시키는 것으로 나타났다. 이러한 결과는 당뇨동물에서 운동이 해마 BDNF 발현의 증가를 통해 인지기능의 손상을 완화시킬 수 있음을 보여주는 것이다.

• Laboraroty Animal Research
• /
• 제34권4호
• /
• pp.239-247
• /
• 2018

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.

• 한국동물번식학회:학술대회논문집
• /
• 한국동물번식학회 2002년도 춘계학술발표대회 발표논문초록집
• /
• pp.84-84
• /
• 2002

This study was to investigate generation of the specific neuronal cell in vitro from the neural progenitors derived from human embryonic stem (hES, MB03) cells. For the neural progenitor cell formation, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for 7-10 days, 20 ng/㎖ of bFGF added N2 medium) from EB. And then for the differentiation into neuronal cells, neural progenitor cells were cultured in N2 medium (without bFGF) supplemented with brain derived neurotrophic factor (BDNF, 5 ng/㎖) or platelet derived growth factor-bb (pDGF-bb, 20ng/㎖) for 2 weeks. (omitted)