羽毛球运动锻炼重构成瘾标志物脑神经源营养因子与体质健康状态的关联性

研究不同种类毒品海洛因(阿片类)和冰毒(精神兴奋剂类)对吸毒人群成瘾标志物血清脑神经源营养因子(Brain-Derived Neurotrophic Factor,BDNF)和体质健康的影响及两者之间的关联性,并进一步探讨羽毛球运动对其关联性的重构效应。选取武汉市青山区青惠居、现代花园等社区的正常人群作为对照组(Control Group,CG组),湖北省某戒毒所和北京某戒毒所的吸毒人群(n=154)作为实验组(Experimental Group,EG组),其中按照吸毒种类的不同将EG组人群分为海洛因组(Heroin Group,HG组)、冰毒组(Methamphetamine Group,MG组),根据是否参与8周羽毛球运动干预进一步将HG组和MG组分为海洛因非运动组HNG组(Heroin No-exercise Group,HNG组)和海洛因锻炼组(Heroin Exercise Group,HEG组),MG组分为冰毒非运动组MNG组(Methamphetamine No-exercise Group,MNG组)和冰毒锻炼组(Methamphetamine Exercise Group,MEG组),所有组别在8周前、后分别采用酶联免疫吸附法ELISA测定血清BDNF的含量和体质健康状态。结果表明:(1)成瘾标志物血清BDNF在脱瘾期、8周常规脱瘾和羽毛球运动呈现应激代偿反应。(2)吸食海洛因或冰毒会对吸毒人群的体质健康状态形成差异化的损伤。(3)吸食海洛因或冰毒人群脱瘾期血清BDNF与体质健康指标密切相关,且这种关联性能被8周羽毛球运动锻炼所重构。(4)羽毛球运动锻炼可以通过增强机体的身体机能和身体素质来改善青少年吸毒人群的体质健康状态并降低成瘾性,适合作为一种戒毒脱瘾的辅助手段予以实践推广。

Beneficial effects of moderate voluntary physical exercise and its biological mechanisms on brain health

This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function, enhancing psychological well-being, decreasing the risks of Alzheimer＇s disease （AD） and dementia, and promoting the effects of antidepressant and anxiolytic. The possible underlying neurobiological mechanisms are involved up-active and down-active pathways. The up-active pathway is associated with enhancements of several neurotransmitters systems afferent to hippocampus, including norepinephrine （NE）, serotonin （5-Hydroxytryptamine, 5-HT）, acetylcholine （ACh） and γ-aminobutyric acid （GABA）. The down-active pathway is mainly concerned with up-regulation of the brain-derived neurotrophic factor （BDNF） and neurogenesis. It is suggested that NE activation via β-adrenergic receptors may be essential for exercise-induced BDNF up-regulation. The possible intracellular signaling pathways of NE-mediated BDNF up-expression may be involved in GPCR-MAPK-PI-3K crosstalk and positive feedback.

Brain-derived neurotrophic factor(BDNF) as a potential mechanism of the effects of acute exercise on cognitive performance

The literature shows that improvements in cognitive performance may be observed following an acute bout of exercise. However, evidence in support of the biological mechanisms of this effect is still limited. Findings from both rodent and human studies suggest brain-derived neu- rotrophic factor （BDNF） as a potential mechanism of the effect of acute exercise on memory. The molecular properties of BDNF allow this protein to be assessed in the periphery （pBDNF） （i.e., blood serum, blood plasma）, making measurements of acute exercise-induced changes in BDNF concentration relatively accessible. Studies exploring the acute exercise--pBDNF--cognitive performance relationship have had mixed findings, but this may be more reflective of methodological differences between studies than it is a statement about the role of BDNE For example, significant associations have been observed between acute exercise-induced changes in pBDNF concentration and cognitive performance in studies assessing memory, and non-significant associations have been found in studies assessing non-memory cognitive domains. Three suggestions are made for future research aimed at understanding the role of BDNF as a biological mechanism of this relationship： 1） Assessments of cognitive performance may benefit from a focus on various types of memory （e.g., relational, spatial, long-term）; 2） More finegrained measurements of pBDNF will allow for the assessment of concentrations of specific isoforms of the BDNF protein （i.e., immature, mature）; 3） Statistical techniques designed to test the mediating role of pBDNF in the acute exercise-cognitive performance relationship should be utilized in order to make causal inferences.

Obesity promotes oxidative stress and exacerbates blood-brain barrier disruption after high-intensity exercise

Purpose: The purpose of this study was to investigate the effects of obesity and high-intensity acute exercise on oxidant-antioxidant status,neurotrophic factor expression, and blood-brain barrier(BBB) disruption.Methods: Twenty-four healthy, untrained men(12 non-obese(mean 14.9% body fat) and 12 obese subjects(mean 29.8% body fat)) performed20 min of continuous submaximal aerobic exercise at 85% maximal oxygen consumption. Blood sampling was performed to examine the oxidant-antioxidant status(reactive oxygen species(ROS) and superoxide dismutase(SOD)), neurotrophic factors(brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF)), and BBB disruption(S100β and neuron-specific enolase) before and after acute exercise.Results: The obese group showed significantly higher pre-exercise serum ROS levels and significantly lower pre-exercise serum SOD levels than the non-obese group(p < 0.05). Serum ROS, SOD, BDNF, NGF, and S100β levels were significantly increased post-exercise compared with pre-exercise levels in both the non-obese and the obese groups(p < 0.05). The obese group showed significantly higher serum ROS, BDNF, NGF,and S100β levels post-exercise compared to the non-obese group(p < 0.05).Conclusion: Our study suggests that episodic vigorous exercise can increase oxidative stress and blood neurotrophic factor levels and induce disruption of the BBB. Moreover, high levels of neurotrophic factor in the blood after exercise in the obese group may be due to BBB disruption,and it is assumed that oxidative stress was the main cause of this BBB disruption.

P2X4 receptor and brain-derived neurotrophic factor in neuropathic pain

Objective:To investigate whether the activation of p38MAPK is involved in the neuropathic pain induced by P2X4 receptor,and the effects of activated P2X4 receptor and p38MAPK on expression of brain-derived neurotrophic factor (BDNF) in the chronic neuropathic pain.Methods:Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats.The right sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at approximately 1.0 mm intervals with 4-0 silk sutures.The microglia inhibitor minocycline,P2X4 antagonist (TNP-ATP) and p38MAPK inhibitor (SB203580) were intrathecally administered every 12 h,3 d post-chronic constriction injury (CCI).Mechanical nociceptive thresholds were assessed with the paw withdrawal threshold (PWT) to von Frey filaments.The expression of P2X4 and BDNF were assessed by both immunohistochemical analysis and RT-PCR.Results:Intrathecal injection of minocycline or TNP-ATP or SB203580 significantly attenuated CCI-induced mechanical allodynia.The time courses of P2X4 receptor and BDNF expression were increased at all points after CCI and reached a peak level on postoperative d 7.Intrathecal injection of minocycline or TNP-ATP or SB203580 markedly suppressed the increase of CCI-induced P2X4 receptor and BDNF expression in the spinal cord.Conclusion:The activation of P2X4 receptor BDNF pathways contributes to neuropathic pain in CCI rats,and the activation of p38MAPK is involved in the neuropathic pain induced by P2X4 receptor.

The complex role of physical exercise and reactive oxygen species on brain

Reactive oxygen species （ROS） are continuously generated during aerobic metabolism and at moderate level. They play a role in redox signaling, but in significant concentration they cause oxidative damage and neurodegeneration. Because of the enhanced sensitivity of brain to ROS, it is especially important to maintain the normal redox state in different types of neuron cells. In last decade it became clear that regular exercise beneficially affects brain function, and can play an important preventive and therapeutic role in stroke, Alzheimer, and Parkinson diseases. The effects of exercise appear to be very complex and could include neurogenesis via neurotrophic factors, increased capillariszation, decreased oxidative damage, and increased proteolyfic degradation by proteasome and neprilysin. Data from our and other laboratories indicate that exercise-induced modulation of ROS levels plays a role in the protein content and expression of brain-derived neurotrophic factor, tyrosinerelated kinase B （TrkB）, and cAMP response element binding protein, resulting in better function and increased neurogenesis. Therefore, it appears that exercise-induced modulation of the redox state is an important means, by which exercise benefits brain function, increases the resistance against oxidative stress, facilitates recovery from oxidative stress, and attenuates age-associated decline in cognition.

The expressions of brain-derived neurotrophic factor and nerve growth factor in purified rat choroid plexus epithelial cells in vitro

Objective： To detect the expressions of brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） in purified rat choroid plexus epithelial cells in vitro. Methods： Primary and passage choroid plexus epithelial cells were obtained from newborn, one-day Spragne-Dawley rats. The expressions of BDNF and NGF were measured by qRT-PCR and Western blottingting. The secretions of BDNF and NGF were detected by ELISA. Cell supematants of primary cells, purified cells and passage 1 cells were harvested. Results： The expression of BDNF in the purified cells was significantly lower than that in the primary cells （P〈0.05）, and it in the primary cells and the purified cells was significantly higher than that in the passage 1 cells （P〈0.05）. The expression of NGF was significantly higher in the purified cells than in the primary cells and the passage 1 cells （P〈0.05）. It in the passage 1 cells was significantly higher than that in the primary cells （P〈0.05）. Conclusion： The time of CPECs transplantation for central nervous system diseases should be selected based on their secretory function and features,which could lead to better and more effective treatment.

The neurotrophic factor Artemin promotes the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells

Objective： The aim of this study was to analyze the capacity of Artemin promoting the motility and invasiveness of MIA PaCa-2 pancreatic cancer （PAC） cells. Methods： The PAC cell line MIA PaCa-2 was cultured in vitro and studied using Transwell chamber analysis. The motility and invasiveness ability affected by different concentrations of Artemin and its receptor GFRa3 were determined. Expression level of matrix metalloproteinase-2 （MMP-2）, epithelial cadherin （E-cadherin） were quantitative analysis using RT-PCR and Western blot in MIA PaCa-2 cells stimulated with Artemin and receptor GFRa3. Results： MIA PaCa-2 PAC cell motility and invasiveness was significantly increased with Artemin and its receptor GFRa3 increasing concentrations than control （P 〈 0.01）. 150 ng/mL was the best of both the role of concentration. MMP-2 was increased significantly （t = 6.35, t = 7.32）, while E-cadherin was significantly lower （t = 4.27, t = 5.61）, after affected by the 150 ng/mL Artemin and GFRα3,respectively. The difference was statistically significant compared with the control group （P 〈 0.01）. Conclusion： Artemin and its receptor GFRa3 can promote PAC cell motility and invasiveness ability and contribute to the aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and E-cadherin downregulation expression.

Subchronic Administration of Linalool Decreases Depressive-Like Behaviour in Restrained Rats

Objectives： The aim of this study was to investigate the effect of linalool in chronically stressed rats on their behaviour as related to depressive disorders and BDNF （brain-derived neurotropic factor） protein in the hippocampus. Methods： Either Tween 80 or linalool （50, 160, 500 mg/kg） was intraperitonealty administered to rats, daily, for two weeks. Some rats were housed in home cages but the others were induced with chronic restrained stress （15 min daily）. At the end of the treatment, the rats were assessed for depressive-like behaviour using the forced swimming test. At the end of the behaviour test, the animals were immediately decapitated and the hippocampus of each animal was removed for the measurement of the BDNF protein by ELISA. Result： The immobility time was significantly increased （p 〈 0.05） but time of climbing was significantly decreased （p 〈 0.05）. The restrained rats treated with linalool, 500 mg/kg, displayed immobility times less than those of their controls （p 〈 0.05） while these rats showed significantly more climbing than in the control rats （p 〈 0.05）. Linalool showed no effect on the BDNF protein in the hippocampus. Conclusions： linalool decreases behaviour related to depressive disorders but it has no effect on the BDNF protein in chronic restrained stress.

Clinical observation of acupuncture combined with medication for mild-to-moderate depression

Objective:To discuss the clinical efficacy and plausible mechanism of Tiao Yang Qu Xie(regulating Yang to eliminate pathogenic factors)needling method plus paroxetine in treating mild-to-moderate depression.Methods:Sixty-six patients with mild-to-moderate depression were divided into an observation group and a control group using the random number table method,each consisting of 33 cases.Another 25 healthy subjects were recruited as a healthy group.The control group took oral paroxetine tablets for treatment,and the observation group received additional acupuncture treatment 3 times weekly.Both groups underwent 4-week treatment.Before treatment,after 2-week and 4-week treatment,and 2 weeks after treatment(follow-up),the patients were assessed using the Hamilton depression scale-17-item(HAMD-17),self-rating depression scale(SDS),self-rating anxiety scale(SAS),and traditional Chinese medicine(TCM)pattern element identification scale for depression.The two groups each randomly contributed 25 cases to detect the protein content of brain-derived neurotrophic factor(BDNF)before treatment and after 4-week treatment,and compared with the healthy group.Results:After 2-week treatment,the markedly effective and total effective rates were significantly higher in the observation group than in the control group(P<0.05);after 4-week treatment,the observation group significantly surpassed the control group in comparing the markedly effective rate(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the HAMD-17 total score and sleep disorder factor score were lower in the observation group than in the control group(P<0.05);the anxiety-somatic score was lower in the observation group than in the control group after 2-week treatment(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the observation group was lower than the control group in comparing the scores of SDS,SAS,and TCM pattern element identification scale for depression(P<0.05).After 4-week treatment,the observation group had an increased serum BDNF protein content,higher than that in the control group(P<0.05)and had no significant difference compared to the healthy group(P>0.05).Conclusion:Compared to the use of oral paroxetine alone,acupuncture plus paroxetine can produce more significant efficacy in treating mild-to-moderate depression and act faster in improving sleep disorder and anxiety-somatic symptoms;increasing the serum BDNF protein content may be a part of the mechanism underlying its antidepressant actions.

柴胡加龙骨牡蛎汤对创伤后应激障碍的疗效及机制研究

目的:柴胡加龙骨牡蛎汤(TJ-12)对创伤后应激障碍的疗效及机制。方法:应用ICR小鼠与EL小鼠建立社会失败应激模型,随机分为5组,即模型组及正常对照组、模型+柴胡加龙骨牡蛎汤高、中、低剂量组(1,0.5,0.1 g.kg-1),ig给药,每天1次,连续给药4周。观察条件性恐惧行为,同时用实时RT-PCR法测小鼠海马糖皮质激素受体(GR)及脑神经源性营养因子(BDNF)的基因表达。结果:与正常对照组比较,模型组小鼠出现"僵直"时间百分比延长、海马基因GR与BDNF表达增加,有非常显著性差异。与模型组比较,TJ-12治疗组不仅可以缩短"僵直"时间百分比,且能降低海马BDNF基因的表达,有显著性差异。结论:TJ-12有效治疗创伤后应激障碍可能与调节海马BDNF基因相关。

Effects of eye-acupuncture on the expression of brainderived neurotrophic factor in the brain of rats with cerebral ischemia reperfusion

Objective To observe the effects of eye-acupuncture therapy and bodyacupuncture therapy on the expression of brain-deprived neurotrophic factor （BDNF） in rats with cerebral ischemia reperfusion injury （CIRI）. Methods According to random number table, 48 SD rats were randomly divided into 6 groups, including normal control group （group A）, sham operation group （group B）, model group （group C）, eye-acupuncture group （group D）, non-acupoint of eye-acupuncture group （group E） and body-acupuncture group （group F）, eight rats in each group. Artery infarction reperfusion model were prepared by using suture-occluded method. Liver region, upper energizer area, lower energizer area and kidney region were selected in the group D. Acupuncture was carried out at the point located at 3 mm from the acupoint areas in the group E. Qūchí （曲池 LI 11）, Zúsānl （足三里 ST 36） and other acupoints were selected in the group F. Zea Longa scoring method was utilized for scoring the neural functions of rats; real-time PCR was carried out to examine the expression level of BDNF mRNA in the brain 72 h after ischemia reperfusion; western blot was carried out to examine the expression level of BDNF protein in the brain 72 h after ischemia reperfusion. Results The symptoms of neurologic impairments in the rats of the group D were alleviated in comparison to those in the group C （P0.01）, and the difference between the group D and the group F was not statistically significant （P0.05）; Compared with the group C, the mRNA and protein expression levels of BDNF in the brain of rats in the group D and the group F both increased （P0.01）, but the difference between the group D and the group F was not statistically significant （P0.05）. Conclusion The functions of eye-acupuncture and body-acupuncture in improving cerebral ischemia reperfusion injury are similar, and the functional mechanisms for the two different therapies may be related to the up-regulation of BDNF expression in brain and thus promote the repairing of brain tissues.

Effect of eye acupuncture on the expression of brainderived neurotrophic factor in hippocampus in rats with cerebral ischemia-reperfusion injury

Objective To observe the effects of eye acupuncture on expression of brain-derived neurotrophic factor （BDNF） in the hippocampus of rats after ischemia- reperfusion injury in order to study the mechanisms of eye acupuncture in improving ischemia-reperfusion injury. Methods SD rats were randomly divided into a normal group, a sham-operation group, a model group and an eye acupuncture group, with 8 rats in each. The cerebral ischemia-reperfusion injury model was established by thread occlusion method. Acupuncture at ＂liver＂, ＂upper-jiao＂, ＂lower-jiao＂, and ＂kidney＂ was performed for 20 min in the eye acupuncture group immediateness, 12 h and 23.5 h after the reperfusion. After 24 h of the reperfusion, the neurophysical behaviors were evaluated by Zea Longa neurophysical impairment score; the expression of ischemic hippocampus BDNF mRNA was measured by RT-PCR; the expression of ischemic hippocampus BDNF protein was detected by Western blot technique. Results After reperfusion 24 h, compared with the model group, the neurologic impairment score of the eye acupuncture group decreased significantly （P〈0.01）; the expressions of BDNF mRNA and protein in rat hippocampi after the eye acupuncture therapy were both obviously increased （P〈0.01）. Conclusion The eye acupuncture therapy is beneficial for neurofunctional rehabilitation by promoting the repair of the nerve cell which is induced by increasing hippocampus BDNF expression.

Function of Ca^(2+)-/calmodulin-dependent protein kinase Ⅳ in Ca^(2+)-stimulated neuronal signaling and behavior

The activity of Ca2+/calmodulin-dependent protein kinase IV(Ca MKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation,the activation of Ca MKIV may trigger synaptic modifications and transcriptional responses,both of which are involved in regulating cognitive and emotional behavior.Here,we used Ca MKIV knockout(KO) neurons and mice to examine the function of Ca MKIV in Ca2+-stimulated intracellular signaling and animal behavior,respectively.Following NMDA receptor activation or membrane depolarization,the up-regulation of CREB(c AMP responsive element binding protein) and its target gene Bdnf(brain-derived neurotrophic factor) was intact in cortical neurons obtained from Ca MKIV KO mice.Ca MKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber.Although Ca MKIV KO mice showed normal memory in the standard passive avoidance task,they were defective in learning the temporal dissociative passive avoidance task.As indicated by the light/dark test and marble-burying test data,Ca MKIV KO mice showed less anxiety and normal perseveration.In the voluntary wheel-running test,Ca MKIV KO mice showed normal running time and distance but higher maximal running speed.Our results demonstrate the function of Ca MKIV in regulating different forms of fear memory,anxiety,and certain aspect of motor function.

Effect of electroacupuncture on brain-derived neurotrophic factor mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury

OBJECTIVE： This work aims to observe the effects of electroacupuncture on brain-derived neuro- trophic factor （BDNF） mRNA expression in mouse hippocampus following cerebral ischemia-reperfu- sion injury. METHODS： The models of mouse cerebral isch- emia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, mod- el ＋ electroacupuncture, and mode ＋ hydergine groups. Mice in the model ＋ electroacupuncturegroup were treated through electroacupuncture at the Shenshu （BL 23）, Geshu （BL 17）, and Baihui （GV 20） acupoints. Mice in the model＋hydergine group were intragastrically administered with hy- dergine （0.77 mg/kg-1.day-l）. The levels of BDNF mRNA expressions in the hippocampus were ana- lyzed through a semi-quantitative reverse transcrip- tion-polymerase chain reaction assay on days 1 and 7 after the surgeries. RESULTS： BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group （both P〈0.01）. On days 1 and 7 of the electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the mod- el ＋ electroacupuncture group was significantly ele- vated compared with the model group （both P〈 0.01） or the model ＋ hydergine group （both P〈 0.01）. On days 1 and 7 of the hydergine treatment, BDNF mRNA expression in the mouse hippocam- pus of the model ＋ hydergine group tended to in- crease compared with the model group; however, statistical significance was not achieved （both P〉 0.05）. CONCLUSION： Electroacupuncture treatment en- hances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.

Anti-depression effects of electroacupuncture through up-regulating serum E_2 and BDNF and expression of BDNF in hippocampus in chronic depression rats

Objective：To investigate the effects of electroacupuncture （EA） at acupoints Baihui （GV 20）, Neiguan （PC 6） and Sanyinjiao （SP 6） on the levels of estradiol （E2） and brain-derived neurotrophic factor （BDNF） in serum, as well as the expression of BDNF in hippocampus in chronic depression rat models. Methods：Thirty female Wistar rats were randomly divided into three groups, including a normal control （NC） group, a model group and an EA group, 10 rats in each group. The depression model was established by using chronic unpredicted mild stress （CUMS）, such as cold-water swimming, tail clamping, electric shock to foot, etc., combined with individual caging for 21 d. Rats in the model group and EA group were randomly exposed to one of the 9 stressors each day and caged individually. After modeling, rats in the EA group were then treated with EA at Baihui （GV 20）, Neiguan （PC 6） and Sanyinjiao （SP 6） once daily for 14 d, and the model group was not treated with EA but bounded in the same way as the EA group. Serum E2 was measured by radioimmunoassay and BDNF was assessed by an enzyme-linked immunosorbent assay （ELISA） and the expression of BDNF in hippocampus was detected by using immunohistochemistry. Results：After the stress stimulation, compared with the NC group, the model group and EA group showed a significant reduction of sucrose preference rate （P〈0.01） and remarkable increase of forced-swimming immobility time （P〈0.01）. In addition, EA significantly reduced the depression-like behavior of rats in the EA group （P〈0.01）. The expressions of E2 and BDNF in serum as well as the expression of BDNF in hippocampus were remarkably lower in the model rats than those in the NC group （P〈0.01,P〈0.01,P〈0.05）. The expression of BDNF in rats’ serum and hippocampus in the EA group was significantly higher than that in the model group （P〈0.05）, while serum E2 increased but insignificantly （P〉0.05）. Conclusion：E2 and BDNF may contribute to the depression-like behaviors of the rats during CUMS period. EA may exert its anti-depression effects through promoting BDNF expression in serum and hippocampus.

Stem cells modified by brain-derived neurotrophic factor to promote stem cells differentiation into neurons and enhance neuromotor function after brain injury

Objective： To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor （BDNF） induction. Methods： Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells （UCMSCs）. Enzyme linked immunosorbent assay （ELISA） was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase （NSE） and glial fibrillary acidic protein （GFAP）, and the number of apoptosis cells were compared respectively. Results： The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly （P〈0.05）, but GFAP-positive cells decreased in BDNF- UCMSCs group compared with the other two groups （P〈0.05）. At the site of high expression of BDNF, the number of apoptosis cells decreased markedly. Conclusion： BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury.

BDNF rescues prefrontal dysfunction elicited by pyramidal neuron-specific DTNBP1 deletion in vivo

Dystrobrevin-binding protein 1 （Dtnbp1） is one of the earliest identified schizophrenia susceptibility genes. Reduced expression of DTNBP1 is commonly found in brain areas of schizophrenic patients. Dtnbp1-nuU mutant mice exhibit abnormalities in beha- viors and impairments in neuronal activities. However, how diminished DTNBP1 expression contributes to clinical relevant fea- tures of schizophrenia remains to be illustrated. Here, using a conditional Dtnbp1 knockout mouse line, we identified an in vivo schizophrenia-relevant function of DTNBP1 in pyramidal neurons of the medial prefrontal cortex （mPFC）. We demonstrated that DTNBP1 elimination specifically in pyramidal neurons of the mPFC impaired mouse pre-pu[se inhibition （PPI） behavior and reduced perisomatic GABAergic synapses. We further revealed that loss of DTNBP1 in pyramidal neurons diminished activity- dependent secretion of brain-derived neurotrophic factor （BDNF）. Finally, we showed that chronic BDNF infusion in the mPFC fully rescued both GABAergic synaptic dysfunction and PPI behavioral deficit induced by DTNBP1 elimination from pyramidal neurons. Our findings highlight brain region- and cell type-specific functions of DTNBP1 in the pathogenesis of schizophrenia, and under- score BDNF restoration as a potential therapeutic strategy for schizophrenia.

Increased basal plasma brain-derived neurotrophic factor levels in sprint runners

Objective Exercise is known to enhance circulating brain-derived neurotrophic factor （BDNF） levels in healthy humans. BDNF changes have been measured in endurance but not in strength exercise. The present study aimed to investigate whether anaerobic activity such as sprinting differentially alters basal plasma BDNF concentration. Methods Brazilian sprinters （100 m） at either the international （Olympics and Outdoor World Championships） （n = 14） or the domestic level （n = 8）, and sedentary subjects （n = 15）, were recruited. Plasma BDNF concentrations were analyzed by enzyme-linked immunosorbent assay. Results The basal plasma BDNF concentrations were significantly higher in the international and the domestic sprinters than in the sedentary subjects. In addition, sprinters at the international level had higher plasma BDNF concentrations than those at the domestic level. Conclusion Our findings suggest that increased basal plasma BDNF level is related to enhanced exercise performance.

Effect of Tongluojiunao injection made from Sanqi(Radix Notoginseng) and Zhizi(Fructus Gardeniae) on brain microvascular endothelial cells and astrocytes in an in vitro ischemic model

OBJECTIVE: To explore the effect of Tongluojiunao injection(TLJN) prepared with Sanqi(Radix Notoginseng) and Zhizi(Fructus Gardeniae) on the interaction between brain microvascular endothelial cells(BMECs) and astrocytes in an in vitro ischemic model.METHODS: First, an in vitro model of cerebral ischemia in BMECs or astrocytes was established by oxygen-glucose deprivation(OGD). TLJN was used as a medicine of intervention. The OGD-injuredBMECs were cultured in various astrocyte-conditioned media. Cell activity, alkaline phosphatase(AKP) and γ-glutamyl transpeptidase(γ-GT) activity,interleukin-1 beta(IL-1β), and tumor necrosis factor alpha(TNF-α) content in BMECs were determined.Additionally, OGD-injured astrocytes were cultured in various BMEC-conditioned media. Cell activity, as well as expression of brain-derived neurotrophic factor(BDNF) and glial cell-derived neurotrophic factor(GDNF) in astrocytes, were detected.RESULTS: The results of paracrine signaling of normal BMECs or astrocytes showed a protective effect on each other: conditioned media from normal astrocytes improved cell viability, AKP, and γ-GT activity, and reduced IL-1β and TNF-α content of injured BMECs; conditioned media from normal BMECs improved cell viability and expression of BDNF and GDNF in injured astrocytes. However, once the BMECs or astrocytes were injured by OGD, the protective effect decreased or disappeared. The above-mentioned protective induction was effectively recovered by TLJN intervention.CONCLUSION: The therapeutic benefit of TLJN was achieved by recovering two-way induction between BMECs and astrocytes, enhancing activity of injured BMECs and astrocytes, stabilizing enzymatic barriers, promoting expression of neurotrophic factors, and inhibiting inflammatory cytokines.