• Title/Summary/Keyword: Brain Derived Neurotrophic Factor

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Antidepressant effect of water extract of Taraxacum platycarpum through BDNF, ERK and CREB pathway (BDNF, ERK 및 CREB 경로를 통한 포공영 추출물의 항우울 효과)

  • Gu, Pil Sung;Lee, Jihye;Choi, Yun Hee;Jung, Ji Wook
    • The Korea Journal of Herbology
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    • v.30 no.3
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    • pp.13-17
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    • 2015
  • Objectives : Taraxacum platycarpum H. Dahlstedt has been reported to have several biological properties such as skin hydration and antiinflammation. The purpose of this study was to examine the antidepressive effects of water extract of T. platycarpum (WTP) on an animal model of depression. Methods : In the present study, normal ICR mice (4 weeks) were used, and orally administered with WTP (25, 50 and 100 mg/kg). Depression-like behavior was monitored the forced swimming test (FST) and tail suspension test (TST) in mice. The locomotor activity was evaluated to eliminate the false-positive activity in the open field test (OFT). Fluoxetine, the selective serotonin reuptake inhibitor, as a positive control was intraperitoneally administered at a dose of 15 mg/kg at 30 min before starting the behavioral test. Moreover, we evaluated the effects of WTP on the expression of brain-derived neurotrophic factor (BDNF) and the extracellular signal-regulated kinase (ERK)/ cyclic AMP response-element binding protein (CREB) signaling pathway in the hippocampus using Western blot. Results : The administration of WTP (50 and 100 mg/kg) significantly (P < 0.05, respectively) reduced the immobility time during FST and TST without accompanying changes in locomotor activity by OFT. Furthermore, WTP at dose of 100 mg/kg increased the BDNF expression and the phosphorylation of ERK and CREB in the hippocampus region. Conclusions : These results suggest that WTP has a useful anti-depressant effect through the regulation of BDNF/ERK/CREB signaling pathway.

Effects of Rotarod Exercise and Electroacupuncture on Muscle Activity and Serum BDNF Level in the Ataxic Rats by the 3-Acetylpyridine (3-Acetylpyridine에 의한 운동실조 동물모델에서 로타로드 운동과 전침이 근활성도와 혈청 BDNF에 미치는 영향)

  • Rho, Min-Hee;Park, Sook-Young
    • The Journal of the Korea Contents Association
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    • v.10 no.4
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    • pp.236-246
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    • 2010
  • The 3-Acetylpyridine(3-AP) induces cerebellar injury which is chemoablation of the inferior olive nucleus. The purpose of this study was to investigate the effects of exercise(Ex) and electroacupuncture(EA) on muscle activity of hindlimb and serum brain derived neurotrophic factor(BDNF) in the ataxia rats by the 3-AP. 12-week-aged male Sprague-Dawley rats were randomly divided into the 5 groups: Control, 3-AP, 3-AP+Ex, 3-AP+EA and 3-AP+Ex+EA groups. Maximal Height Vertical Jump(MHVJ) was significantly decreased in the 3-AP compared with control group, and it was increased in Ex, EA and Ex+EA groups than 3-AP group. The muscle activity of hindlimb was significantly increased in the 3-AP groups than control group, also it was most decreased in Ex+EA group. The concentration of BDNF of the serum was significantly decreased in the Ex, EA and Ex+EA groups than 3-AP group. The results of this study showed that dynamic exercise and electroacupuncture have a positive effect on functional recovery and in the ataxia rats by the 3-AP.

Review of the Neuroscientific Evidences for the People With Schizophrenia (조현병 환자의 신경과학적 근거에 대한 고찰)

  • Shin, Eun-Sik
    • Therapeutic Science for Rehabilitation
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    • v.2 no.1
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    • pp.5-12
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    • 2013
  • The purpose of this review is to address the flow of current neuroscientific researches and to provide for the clinicians with therapeutic evidences for schizophrenia which can help them clinical decision making. Since the very beginning, a lot of scientific studies about schizophrenia have been undertaken. In this review, I describes the evidences focused on development of schizophrenia including neurobiological dysfunction, neurodevelopmental model, Kalirin, and Brain-Derived Neurotrophic Factor(BDNF) and neuroanatomic abnormalities based on neuroimaging studies. In conclusion, schizophrenia influencing on broad impairment of human function such as activities of daily life, occupations, and relationships has been studied underlying causes and treatments, but still remained uncertainty. However, there are plenty of useful evidences available for the clinicians to make a good therapeutic choice.

Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum

  • Asrari, Najmeh;Yazdian-Robati, Rezvan;Abnous, Khalil;Razavi, BiBi Marjan;Rashednia, Mrazieh;Hasani, Faezeh Vahdati;Hosseinzadeh, Hossein
    • Journal of Pharmacopuncture
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    • v.21 no.1
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    • pp.35-40
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    • 2018
  • Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum. Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis. Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant. Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

DEPRESSION: CELLULAR AND PHYSIOLOGICAL CONSEQUENCES OF STRESS (ANTIDEPRESSANT EFFECT OF SEROTONIN N-ACETYLTRANSFERASE INHIBITOR)

  • Kim Kyong-Tai
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2001.12a
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    • pp.22-37
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    • 2001
  • Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. Serotonin N-acetyltransferase (AA-NAT) which is found to be expressed in pineal gland, retina, and various tissues, catalyses the conversion of serotonin to N-acetylserotonin and is known as the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AA-NAT can be used to treat serotonin-and melatonin-related diseases such as insomnia, depression and seasonal affective disorders (SAD). Several assay methods have been developed by which to measure AA-NAT activity. We have also developed a simple, rapid and sensitive AA-NAT assay method that takes advantage of differences in the organic solubilities between acetyl CoA and N-acetyltryptamine. We screened modulators of AA-NAT activity from the water extracts of the medicinal plants. We found MNP1005 which strongly inhibited the activity of AA-NAT ($IC_{50}$=2.2$\mu$M). Enzyme inhibitory kinetic studies revealed that MNP1005 exhibited a noncompetitive inhibition toward tryptamine. The antidepressant effect of MNP1005 was investigated on behavioral despair test so called forced swimming test (FST). MNP1005 significantly increased swimming behavior by reducing immobility with treatment of 10 mg/kg when compared to the vehicle-treated control group (P < 0.05). This suggests that MNP1005 possesses antidepressant activity. The influence of chronic MNP1005 treatment on the expression of brain-derived neurotrophic factor (BDNF) was examined by in situ hybridization and Northern blot. Chronic treatment of MNP1005 blocked the downregulation of BDNF mRNA in the frontal cortex and other cortex regions in response to restraint stress.

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ADENOVIRAL VECTOR MEDIATED IN VIVO GENE TRANSFER OF BDNF PROMOTE FUNCTIONAL RECOVERY AFTER FACIAL NERVE CRUSH INJURY (안면신경 압박손상 후 Adenovirus 매개 BDNF 유전자 전달을 통한 신경손상 회복에 관한 연구)

  • Yang, Byoung-Eun;Lee, Jong-Ho
    • 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.

Association between BDNF and Antidepressant Effects of Exercise in Youth: A Preliminary Study (아동청소년에서 운동의 항우울 효과와 BDNF와의 관련성에 대한 예비 연구)

  • Lim, You Bin;Kim, Jun Won;Hong, Soon-Beom;Kim, Jae-Won
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.27 no.1
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    • pp.72-81
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    • 2016
  • Objectives: The purpose of this study was to evaluate anti-depressive effects of exercise on child and adolescent and its association with brain derived neurotrophic factor (BDNF). Methods: Twenty nine middle school boys (age $13.3{\pm}0.7$) were divided into two groups, 15 boys for control group and 14 in the experimental group. The control group participated in a regular exercise program, 3 times a week for 15 weeks. During the same period, the experimental group participated in an aerobic exercise program specifically designed to enhance anti-depressive effect of exercise. Serum BDNF level and its performance of each group on the Beck Depression Index (BDI), Children's Depression Inventory (CDI), Screen for Child Anxiety Related Emotional Disorders (SCARED), Aggression Questionnaire (AK-Q), and Stroop task were compared before and after the exercise program. Results: Scores of BDI, CDI, SCARED, and AK-Q were significantly lower in both groups after the exercise programs compared to those before the programs. The Stroop task performances were significantly improved after the programs. However, there were no significant differences between two exercise programs, except SCARED separation anxiety, AK-Q physical, and verbal aggression scores. Also, no association was found between serum BDNF level and anti-depressive effects of exercise. Conclusion: Our preliminary results suggest a possible effect of exercise on depression, anxiety, aggression, and cognition of child and adolescents.

Effect of Sihogayonggolmoryeotang on SPS-induced PTSD in Rats (시호가룡골모려탕(柴胡加龍骨牡蠣湯)이 흰쥐에서 SPS로 유도된 PTSD에 미치는 효과)

  • Kim, Hwi-Yeol;Lee, Tae Hee
    • Herbal Formula Science
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    • v.27 no.2
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    • pp.121-136
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    • 2019
  • Objective : To investigate the effect of sihogayonggolmoryeotang (SY) on Single Prolonged Stress(SPS)-induced Post Traumatic Stress Disorder(PTSD). Method : To confirm the effects of SY on SPS-induced PTSD, Changes in body weight, sucrose intake open field test(OFT) and forced swimming test(FST)were observed. After behavioral tests, the plasma corticosterone(CORT) from the abdominal aorta, serotonin(5-HT) from prefrontal cortex, hippocampus, amygdala and striatum, norepinephrine(NE) and dopamine(DA) from hippocampus was measured by ELISA. mRNA expression of brain-derived neurotrophic factor(BDNF) and cAMP response element-binding protein(CREB) in hippocampus was measured by RT-PCR. Result : Weight change and sucrose intakes of rats in 14th day after the administration of SY were significantly increased in the SPS + SY450 group compared to the SPS group (p<0.05). Numbers of crossing in the central zone in the OFT were significantly increased in the SPS + SY450 group (p<0.05) compared with the SPS group. The immobility time of FST was significantly decreased in SPS + SY450 group compared with SPS group (p<0.05). The change of plasma CORT concentration was significantly decreased in SPS + SY450 group compared with that in SPS group (p<0.05). The change of 5-HT concentration was significantly increased in the SPS + SY450 group at hippocampus and amygdala compared with the SPS group (p<0.05). The concentration of DA was significantly increased in the SPS + SY450 group compared with the SPS group (p<0.05). The expression of BDNF and CREB were significantly increased in SPS + SY450 group compared with the SPS group (p<0.05). Conclusion : SY administration lowered the increase of CORT caused by PTSD and increases the 5-HT concentration and reversed the decreased expression of NE and DA and BDNF and CREB by PTSD. It is postulated that SY is effective in treating PTSD by restoring cognitive function, memory impairment, unstable emotional disturbances.

Effect of Astragali Radix on SPS-induced PTSD in Rats (황기(黃芪)가 흰쥐에서 SPS로 유도된 PTSD에 미치는 효과)

  • Min, Ye-Eun;Lee, Tae-Hee
    • Herbal Formula Science
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    • v.30 no.3
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    • pp.109-121
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    • 2022
  • Objective : This study is conducted to investigate the effect of Astragali Radix on Post Traumatic Stress Disorder(PTSD) induced by the Single Proposed Stress(SPS). Methods : The experiment was conducted with five groups; SAL groups with only saline treatment, SPS group, SPS + ARX25 group, SPS + ARX50 group, and SPS + ARX100 group. After applying SPS, saline and ARX were administered for 14 days to identify the change of body weight, sucrose intake amount, and behavioral changes through Open Field Test(OFT) and Forced Swimming Test(FST). After the behavioral experiment, plasma corticosterone levels, serotonin, norepinephrine and dopamine concentrations were measured by enzyme-linked immunoassay in medical prefrontal cortex, hippocampus, and amygdala. Brain-derived neurotrophic factor(BDNF) in the hippocampus was measured using Reverse Transcription Polymerase Chain Reaction. Results : Weight change has significantly decreased in the SPS group compared to the SAL group(p<0.05). On day 14, the sucrose intake of rats has significantly increased in the SPS + ARX100 group compared to the SPS group(p<0.05). In OFT, the number of staying in the central space has significantly increased in the SPS + ARX100 group(p<0.01). In FST, immobility has significantly decreased in SPS + ARX50 group and SPS + ARX100 group(p<0.05). The concentration of serotonine, dopamine and BDNF expression has increased significantly in SPS + ARX100 group compared to SPS group(p<0.05) Conclusions : In the SPS-induced PTSD experiment, ARX increased sucrose intake and the numbers of crossing in the central zone space in OFT, decreased immobility time in FST, and increased concentration of serotonin, dopamine, and BDNF. It can be postulated that the ARX could be effective for the treatment of PTSD.

A Neuroprotective Action of Quercetin and Apigenin through Inhibiting Aggregation of Aβ and Activation of TRKB Signaling in a Cellular Experiment

  • Ya-Jen Chiu;Yu-Shan Teng;Chiung-Mei Chen;Ying-Chieh Sun;Hsiu Mei Hsieh-Li;Kuo-Hsuan Chang;Guey-Jen Lee-Chen
    • 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.