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1.
目的 观察温阳解郁颗粒(Wenyang Jieyu granule,WYJY)对皮质酮(Corticosterone,CORT)诱导损伤型小鼠海马神经细胞(TH22 cell)的保护作用,基于脑源性神经营养因子(Brain derived neurotrophic factor, BDNF)/酪氨酸激酶B(Tyrosine kinase B, TrkB)/细胞外信号调节蛋白激酶(Extra cellular regulated protein kinases, ERK)信号通路探讨WYJY保护海马神经细胞的作用机制。方法 体外构建小鼠海马神经细胞皮质酮诱导损伤模型,以不同浓度的WYJY和氟西汀(Fluoxetine,FXT)含药血清作用于模型细胞,细胞增殖-毒性检测(Cell Counting Kit-8, CCK-8)法分析细胞活性,倒置显微镜下观察给药前后细胞形态结构的改变,采用蛋白免疫印迹法(Western Blot)、实时荧光定量PCR(Quantitative real-time PCR, qPCR)法检测神经细胞内凋亡因子(BCL2-Associated X, Bax)、抗凋亡因子(B-cell lymphoma-2, Bcl-2)、BDNF、Trkb、ERK以及丝氨酸/苏氨酸激酶(Phospho-p90RSK, RSK)、环磷腺苷效应元件结合蛋白(cAMP-response element binding protein, CREB)蛋白表达水平以及相关基因的表达水平。结果 在浓度为459.5 μmol·L-1的CORT作用24 h后,HT22细胞的活性抑制率达到50%,在此条件作用下细胞形态结构损伤明显,凋亡程度严重,细胞上清中BDNF的含量显著减少(P<0.05),细胞内凋亡相关因子Bax/Bcl-2的比值明显升高(P<0.01),BDNF、Trkb、ERK、RSK、CREB磷酸化蛋白表达水平和mRNA表达水平明显降低(P<0.01);以5%的浓度为2.85 g·kg-1的WYJY和10%的FXT含药血清作用于受损的HT22细胞后,HT22细胞存活率明显提升(P<0.01),细胞结构的损伤明显改善,细胞凋亡程度减轻,细胞外BDNF的含量显著升高(P<0.05),细胞内Bax/Bcl-2比值显著下调(P<0.01),BDNF、Trkb、ERK、RSK、CREB磷酸化蛋白表达水平和mRNA表达水平显著提升(P<0.05,P<0.01)。结论 温阳解郁颗粒可有效保护高浓度CORT造成的小鼠海马神经细胞损伤。调控BDNF/Trkb/ERK通路,放大CREB信号传导,影响Bcl-2、BDNF水平,可能是其保护海马神经元,发挥抗抑郁疗效的重要机制。  相似文献   
2.
《Immunobiology》2022,227(3):152211
ObjectiveThe present study was intended to investigate the role of embryonic stem cell-derived exosomes (ESC-Exos) in Müller cell retrodifferentiation and their specific mechanism.MethodsFollowing co-incubation of the extracted ESC-Exos and Müller cells, their effects on the retrodifferentiation and proliferation of Müller cells were measured by EdU staining, immunofluorescence, and western blot. ESCs transfected with small interfering RNA of BDNF were co-incubated with Müller cells to determine Müller cell proliferation and retrodifferentiation. β-catenin expression in the nucleus and GSK-3β phosphorylation were measured to determine the role of the Wnt pathway in Müller cells. The function of the retina in RCS rats was observed using flash electroretinogram.ResultsCo-incubation of ESCs with Müller cells or overexpression of BDNF contributed to Müller cell retrodifferentiation and proliferation, as evidenced by increased cell proliferation, fluorescence intensities of proliferation markers and retinal stem cell markers, and expression of BDNF and β-catenin, and suppressed GSK-3β phosphorylation. However, co-incubation with ESCs silencing BDNF or treatment with GW4869 inhibited the proliferation and retrodifferentiation of retinal Müller cells. In addition, exosome injection increased BDNF, BrdU, PH3, SOX2, and Pax6 expression, enhanced β-catenin expression in the nucleus, diminished GSK-3β, and improved retinal degeneration in RCS rats.ConclusionESC-Exos accelerated Müller cell retrodifferentiation and proliferation through Wnt pathway activation by delivering BDNF protein to Müller cells.  相似文献   
3.
目的:观察大补元煎对APP/PS1痴呆小鼠海马突触可塑性及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的作用,并探讨其改善突触可塑性的可能机制。方法:将APP/PS1小鼠36只分为模型组、多奈哌齐组(6.5×10~(-4)g·kg~(-1)·d~(-1))和大补元煎组(13.2 g·kg~(-1)·d~(-1)),野生鼠12只设为正常组,正常组和模型组给予等体积生理盐水,各组连续灌胃30 d。应用Morris水迷宫检测各组小鼠的学习记忆能力,应用尼氏染色和高尔基染色观察海马区神经元和突触的病理形态变化,应用免疫荧光(IF)观察海马突触后致密蛋白95(PSD95)及突触素(SYN)的蛋白表达水平,采用蛋白免疫印迹法(Western blot)检测海马中BDNF,TrkB,CREB及磷酸化CREB(p-CREB)的蛋白表达水平。结果:与空白组比较,模型组小鼠平台潜伏期和游泳总路程增加(P0.01),穿越平台次数和目标象限停留时间减少(P0.01),小鼠海马CA3区神经元胞内尼氏体减少或消失,小鼠海马CA3区神经元及树突分支数量、树突棘密度减少(P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平减少(P0.01)。与模型组比较,多奈哌齐组和大补元煎组小鼠平台潜伏期和游泳总路程减少(P0.05,P0.01),穿越平台次数和目标象限停留时间增加(P0.05,P0.01),小鼠海马CA3区神经元胞内尼氏体数量增多,小鼠海马CA3区神经元及树突分支数量,树突棘密度增加(P0.05,P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平增加(P0.05,P0.01)。结论:大补元煎改善APP/PS1双转基因小鼠突触可塑性的机制可能与其上调小鼠海马中BDNF/TrkB/CREB信号通路有关。  相似文献   
4.
目的研究甘麦大枣汤对抑郁症模型大鼠前额叶和杏仁核中脑源性神经营养因子(BDNF)、5-羟色胺转运体(SERT)基因表达及血清5-羟色胺(5-HT)水平的影响。方法将40只Wistar雄性大鼠随机分为正常组、模型组、甘麦大枣汤组和盐酸氟西汀组,每组10只。除正常组外,其余各组以慢性不可预见性温和刺激配合孤养的方法制备抑郁症模型。造模后,甘麦大枣汤组灌胃给予甘麦大枣汤浓缩药液(12.5 ml/kg),盐酸氟西汀组灌胃给予盐酸氟西汀药液(10 ml/kg),正常组和模型组灌胃给予蒸馏水2 ml。各组均干预28天,气相色谱-质谱联用检测血清5-HT水平,实时荧光定量PCR检测大鼠前额叶及杏仁核中BDNF mRNA、SERT mRNA的相对表达量。结果①与正常组比较,模型组大鼠血清5-HT水平降低(P0.05),前额叶及杏仁核中BDNF mRNA、SERT mRNA相对表达量减少(P0.05)。②与模型组比较,甘麦大枣汤组、盐酸氟西汀组大鼠血清5-HT水平升高(P0.05);甘麦大枣汤组大鼠前额叶中BDNF mRNA相对表达量增加(P0.05),盐酸氟西汀组大鼠前额叶中BDNF mRNA和SERT mRNA相对表达量增加(P0.05);甘麦大枣汤组、盐酸氟西汀组大鼠杏仁核中BDNF mRNA、SERT mRNA相对表达量增加(P0.05)。③与盐酸氟西汀组比较,甘麦大枣汤组大鼠血清5-HT水平,前额叶及杏仁核中BDNF mRNA、SERT mRNA的相对表达量差异无统计学意义(P0.05)。结论甘麦大枣汤可能通过升高血清5-HT水平、增加前额叶和杏仁核中BDNF mRNA及杏仁核中SERT mRNA的表达,对抑郁症发挥干预作用。  相似文献   
5.
越鞠丸联合盐酸氟西汀胶囊治疗抑郁症临床研究   总被引:3,自引:0,他引:3  
兰建萍  蒋晁明  郑顺 《新中医》2020,52(3):29-31
目的:观察越鞠丸联合盐酸氟西汀胶囊治疗抑郁症的临床效果及对血清脑源性神经营养因子(BDNF)水平的影响。方法:纳入因抑郁症就诊的64例患者,随机分为对照组与治疗组各32例。对照组给予盐酸氟西汀胶囊抗5-羟色胺(5-HT)治疗,治疗组在对照组基础上联合越鞠丸治疗。比较2组治疗前后汉密尔顿抑郁量表(HAMD-24)评分、抑郁症状学快速自评量表(QIDS-SR16)、血清BDNF水平及总体疗效。结果:治疗前后比较,2组HAMD-24评分、QIDS-SR16评分均下降,血清BDNF水平升高(P<0.05),组间比较,治疗组2项评分下降更多,血清BDNF水平升高更多(P<0.05)。治疗后,治疗组总体疗效为90.63%,优于对照组的68.75%,差异有统计学意义(P<0.05)。结论:越鞠丸联合盐酸氟西汀胶囊治疗抑郁症,可更加有效减缓患者抑郁症状,升高血清BDNF水平,增加临床疗效,有效保护患者脑功能,值得临床推广。  相似文献   
6.
Brain‐derived neurotrophic factor (BDNF), traditionally known for promoting neuronal growth and development, is also a modulator of synaptic transmission. In addition to the well‐characterized effects at excitatory synapses, BDNF has been shown to acutely suppress inhibitory neurotransmission; however, the underlying mechanisms are unclear. We have previously shown that at inhibitory synapses in layer 2/3 of the somatosensory cortex, BDNF induces the mobilization of endogenous cannabinoids (eCBs) that act retrogradely to suppress GABA release. Here, we hypothesized that in the hippocampus, BDNF acts similarly via eCB signaling to suppress GABAergic transmission. We found that the acute application of BDNF reduced the spontaneous inhibitory postsynaptic currents (sIPSCs) via postsynaptic TrkB receptor activation. The suppressive effects of BDNF required eCB signaling, as this effect on sIPSCs was prevented by a CB1 receptor antagonist. Further, blocking the postsynaptic eCB release prevented the effect of BDNF, whereas eCB reuptake inhibition enhanced the effect of BDNF. These results suggest that BDNF triggers the postsynaptic release of eCBs. To identify the specific eCB release by BDNF, we tested the effects of disrupting the synthesis or degradation of 2‐arachidonoylcglycerol (2‐AG). Blocking 2‐AG synthesis prevented the effect of BDNF and blocking 2‐AG degradation enhanced the effect of BDNF. However, there was no change in the effect of BDNF when anandamide degradation was blocked. Collectively, these results suggest that in the hippocampus, BDNF‐TrkB signaling induces the postsynaptic release of the endogenous cannabinoid 2‐AG, which acts retrogradely on the presynaptic CB1 receptors to suppress GABA release.  相似文献   
7.
The increasing prevalence of stress-related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single-group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy-one in-patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)-10 were included in the study. In addition to symptomatology, the stress-responsive biomarkers heart rate variability (HRV) and serum brain-derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6-week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered.  相似文献   
8.
Infertile women often experience chronic stress, which may have a negative impact on general well‐being and may increase the burden of infertility. In this open‐label, parallel, randomized controlled trial, infertile women aged 18–50 years (median 37 years) were assigned to an 8‐week mindfulness‐based program (MBP) or no intervention. The primary outcome was stress severity measured by the Lipp's Stress Symptoms Inventory (ISSL). Data were analyzed by modified intent‐to‐treat principle, which included all cases available to follow‐up regardless of adherence to the intervention (62 participants from the MBP group and 37 from the control group). The median number of symptoms of chronic stress recorded in the past month decreased from six (interquartile range 2 to 9) before the MBP to two (interquartile range 1 to 4) after the intervention (p < 0.001, repeated measures analysis of variance with Time × Group interaction). Depressive symptoms also decreased after MBP, whereas general well‐being improved (p < 0.01 for both outcomes). Hair cortisol and serum brain‐derived neurotrophic factor (BDNF) did not change significantly between preintervention and postintervention. None of the outcomes changed significantly in the control group. MBP was effective in reducing stress and depressive symptoms while increasing general well‐being in infertile women.  相似文献   
9.
《Molecular therapy》2022,30(2):519-533
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10.
BackgroundPhysiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear.ObjectiveThis study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients.MethodsWe included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO2peak. Before and after interventions, we evaluated VO2peak, peak CO, arteriovenous oxygen difference (AV O2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O2Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites).ResultsHIIT induced significant increases in VO2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P < 0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P = 0.012) with prominent redistribution of mitochondria.ConclusionAs compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O2 extraction in stroke patients. Increased cerebral O2 utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT.ClinicalTrials.gov identifierNCT04135391.  相似文献   
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