电针对阿尔茨海默病模型大鼠海马区BDNF TrkB的影响

目的:观察电针对阿尔茨海默病(AD)模型大鼠海马区BDNF、TrkB的影响,探讨针刺风府穴治疗AD的作用机理。方法:选取Wistar大鼠,随机分为正常组、假手术组、模型组、电针组,以双侧海马注射微量Aβ25-35制备AD动物模型,电针组选取风府穴行电针治疗,以Morris水迷宫评价大鼠学习记忆能力,免疫组化法观察海马区BDNF、TrkB的表达。结果:与正常组比较,模型组学习记忆能力减退,海马区BDNF、TrkB的表达明显减少(P0.01);经电针治疗后,学习记忆能力增强,BDNF、TrkB的表达较模型组增加。结论:针刺风府穴可显著改善AD模型大鼠的学习记忆能力,增加海马区BDNF、TrkB的表达。     

Brain‐derived Neurotrophic Factor Signaling Mediates the Antidepressant‐like Effect of the Total Flavonoids of Alpiniae Oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice

The present study verified the antidepressant‐like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant‐like effects of AOF in mice. Previous research has shown that tropomyosin‐related kinase B (TrkB) receptor‐mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression‐like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element‐binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant‐like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant‐like effects by targeting TrkB receptor‐mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright © 2016 John Wiley & Sons, Ltd.     

茸菖胶囊对戊四唑点燃模型大鼠海马BDNF及其受体TrkB表达的影响

[目的] 阐明脑源性神经营养因子(BDNF)及其功能受体酷氨酸激酶B(TrkB)在癫痫后认知障碍中的作用以及茸菖胶囊对海马脑源性神经营养因子及其受体TrkB的远期影响.[方法] 以戊四唑点燃大鼠为模型,随机分为中药组?西药组?模型组和正常组,观察致痫大鼠的惊厥发作次数?级别?潜伏期,采用RT-PCR检测BDNF和TrkB基因表达水平.[结果] 各治疗组大鼠与治疗前相比,均可减少大鼠的发作程度,治疗前造模各组的发作次数无统计学差异(P>0.05),茸菖胶囊治疗后,治疗大鼠的发作评分明显下降,与模型组相比,各治疗组的发作评分较低(P<0.05),茸菖胶囊组与丙戊酸钠组的评分无统计学差异(P>0.05).各组海马组织BDNF mRNA表达显示,模型组海马组织BDNF mRNA表达较正常组?中药组和VPA组明显增多,中药组表达较其他各组增多均有统计学差异(P<0.01).海马组织TrkB mRNA表达与BDNF mRNA表达趋势相同.[结论] 茸菖胶囊可以有效控制癫痫大鼠的发作次数及级别,其作用机制与调控海马组织中BDNF?TrkB mRNA的表达有关.     

神经复元方对卒中后抑郁大鼠BDNF/TrkB表达及海马神经元突触可塑性的影响

目的:研究神经复元方对卒中后抑郁(PSD)模型大鼠脑源性生长因子(BDNF)/酪氨酸激酶受体B(TrkB)表达及海马神经元突触可塑性的影响,探讨其改善抑郁症状的作用机制。方法:采用经典的线栓大脑中动脉加用慢性不可预见温和应激结合孤养法,建立PSD大鼠模型,分为假手术组、PSD模型组、氟西汀组、神经复元方低、中、高剂量组。造模成功后干预28 d,比较各组大鼠行为学变化,用荧光定量RT-PCR和蛋白质免疫印迹法检测各组BDNF/TrkB-mRNA及生长相关蛋白-43(GAP-43)及突触素I(SYN I)和突触囊泡素(SYNA)的表达水平,用透射电镜观察海马神经元突触的超微结构。结果:高剂量神经复元方干预后的PSD模型大鼠学习记忆功能提升,海马BDNF和TrkB-mRNA表达比较模型组显著增高,差异有统计学意义(P<0.05),海马神经元突触相关蛋白SYN I和SYNA的表达水平比较模型组明显提高,差异有统计学意义(P<0.05)。高剂量神经复元方组海马神经元突触密度和突触后致密物厚度均显著高于模型组。结论:神经复元方可改善PSD模型大鼠抑郁症状,提升大鼠学习记忆能力,其作用机制可能是通过增加海马BDNF/TrkB的含量,促进海马突触素I和SYNA等突触生长相关蛋白表达,增强PSD模型大鼠海马神经元可塑性而发挥作用。     

基于BDNF/TrkB/PI3K/Akt信号通路的滋肾醒脑汤对阿尔茨海默病大鼠学习记忆能力的影响

目的基于BDNF/TrkB/PI3K/Akt信号通路观察滋肾醒脑汤对阿尔茨海默病(AD)大鼠学习记忆能力的影响,探讨其可能的作用机制。方法采用侧脑室注射β-淀粉样蛋白制备AD大鼠模型,假手术组注射等体积生理盐水,将成模大鼠随机分为模型组、中药组及阳性对照组,每组6只,中药组及阳性对照组分别予滋肾醒脑汤(16.74 g/kg)和盐酸多奈哌齐混悬液(0.45 mg/kg)灌胃,假手术组和模型组灌胃等体积蒸馏水,每日1次,连续4周。采用Morris水迷宫实验进行大鼠行为学检测,TUNEL染色检测海马组织神经细胞凋亡情况,Western blot检测海马组织脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)蛋白表达,免疫组化检测海马组织PI3K、Akt蛋白表达。结果与假手术组比较,模型组大鼠逃避潜伏期明显延长,跨越平台次数减少,目标象限停留时间缩短(P<0.05,P<0.01),海马组织神经细胞凋亡率明显升高,BDNF、TrkB、PI3K、Akt蛋白表达明显降低(P<0.05);与模型组比较,中药组及阳性对照组大鼠逃避潜伏期明显缩短,跨越平台次数增加,目标象限停留时间延长(P<0.01,P<0.05),海马组织神经细胞凋亡率明显降低,BDNF、TrkB、PI3K、Akt蛋白表达明显升高(P<0.05,P<0.01),中药组与阳性对照组差异无统计学意义(P>0.05)。结论滋肾醒脑汤可改善AD大鼠学习记忆能力,其机制可能与上调BDNF/TrkB/PI3K/Akt信号通路蛋白表达,减少神经细胞凋亡有关。     

山茱萸多糖对衰老模型大鼠学习记忆能力及海马突触可塑性的影响

目的:观察山茱萸多糖对衰老模型大鼠学习记忆能力、海马脑源性神经生长因子(BDNF),酪氨酸蛋白激酶B(Trk B)蛋白表达及海马长时程增强(LTP)的影响,并探讨其机制。方法:清洁级SD大鼠40只,随机数字表法分为正常组、模型组、山茱萸多糖低、高剂量组,每组10只,采用D-半乳糖(140 mg·kg~(-1)·d-1)皮下注射构建大鼠衰老模型,同时正常组、模型组每天给予生理盐水、低剂量组和高剂量组给予山茱萸多糖(0.14,0.28 g·kg~(-1)·d-1)灌胃6周。Morris水迷宫检测学习记忆能力,高频刺激海马CA3区Schaffer侧支,在同侧海马CA1区诱导LTP的方法检测大鼠海马神经元突触可塑性的变化,免疫组化法检测海马神经元BDNF和Trk B蛋白的表达情况。结果:与正常组比较,模型组平均逃避潜伏期明显延长,在目标象限内游泳的距离占总距离的百分比和探索次数明显减少,海马LTP幅度显著降低,海马BDNF和Trk B蛋白表达降低(P0.01)。高剂量组与模型组比较平均逃避潜伏期明显降低,在目标象限内游泳的距离占总距离的百分比和探索次数明显升高,海马LTP幅度显著升高,海马BDNF和Trk B蛋白表达升高(P0.01)。结论:山茱萸多糖可通过提高海马BDNF和Trk B的表达及大鼠海马CA1区的LTP,明显改善突触的可塑性,这可能是山茱萸多糖提高学习记忆能力的重要机制之一。     

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant‐like effects. We observed that SD aggravated the anxiety‐like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant‐like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant‐like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.     

Bushenhuoxue improves cognitive function and activates brain-derived neurotrophic factor-mediated signaling in a rat model of vascular dementia

OBJECTIVE: To explore the protective mechanisms of the Traditional Chinese Medicine Bushenhuoxue(BSHX) in a rat model of vascular dementia(VD).METHODS: A rat model of VD was developed using bilateral common carotid artery occlusion(BCCAO).Rats were administered BSHX(10.14 or 5.07 g/kg),nimodipine(11.06 mg/kg; positive control), or saline(control) by gavage daily for 30 d post-surgery.Learning and memory abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using light microscopy(hematoxylin and eosin staining) and transmission electron microscopy(TEM). The m RNA and protein expression levels of brain-derived neurotrophic factor(BDNF), tyrosine receptor kinase B(Trk B), phosphatidyl inositol 3-kinase(PI3 K), serine/threonine kinase(AKT), and c AMP response element binding protein(CREB) were measured by real-time polymerase chain reaction(RT-PCR) and Western blot, respectively.RESULTS: Compared with the sham group, rats with BCCAO exhibited impaired learning and memory abilities(Morris water maze) and showed abnormalities in neuronal morphology(light microscopy)and ultrastructure(TEM) in the hippocampus. They also had decreased m RNA and protein expressions of BDNF, Trk B, PI3 K, AKT, and CREB in hippocampal tissue(all P 0.05). In rats with BCCAO, administration of BSHX attenuated deficits in learning and memory, improved the morphology and ultrastructure of hippocampal neurons, and enhanced m RNA and protein expression levels of BDNF, Trk B, PI3 K,AKT, and CREB(all P 0.05).CONCLUSION: BSHX may protect hippocampal neurons and improve learning and memory abilities, at least in part via the activation of BDNF/Trk B/PI3 K/AKT/CREB signaling.     

合欢花总黄酮对抑郁模型大鼠海马CA3区BDNF和TrkB表达的影响

目的:观察合欢花总黄酮对抑郁模型大鼠海马CA3区脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B(TrkB)表达的影响.方法:将90只SD大鼠随机分为正常组、模型组、盐酸文拉法辛组(12.5 mg·kg-1)、合欢花总黄酮(100,50,25 mg·kg-1)剂量组.应用孤养加慢性不可预见性应激建立抑郁症模型,造模同时ig给药,每天1次,连续给药21 d,正常组、模型组ig等体积蒸馏水.用Morris水迷宫法测定各组大鼠学习记忆能力,免疫组织化法检测大鼠海马CA3区BDNF及TrkB表达.结果:与正常组比较,模型组大鼠Morris水迷宫试验逃避潜伏期时间增加、成功次数减少(P ＜0.05,P＜0.01);海马CA3区BDNF及受体TrkB的表达降低(P＜0.01).与模型组比较,盐酸文拉法辛组、合欢花总黄酮3个剂量组Morris水迷宫试验逃避潜伏期时间缩短、成功次数增加(P＜ 0.05或P＜0.01),海马CA3区BDNF及受体TrkB的表达明显增高(P＜0.05或P＜0.01).结论:合欢花总黄酮能够提高抑郁模型大鼠学习记忆能力,其作用机制可能与增加抑郁模型大鼠海马CA3区BDNF及其受体TrkB的表达,进而保护海马神经元有关.     

补骨脂汤对痴呆大鼠海马NR2B、BDNF/TrkB表达的影响

目的 为探讨补骨脂汤对改善血管性痴呆大鼠的空间学习记忆的机理.方法 用双侧结扎颈动脉反复灌注,用Morris试验测试大鼠的空间学习记忆,RT-PCR测定与学习记忆密切相关的NR2B、BDNF/TrkB基因表达产物.结果 补骨脂汤高、低剂量组的逃避潜伏期都明显短于模型组(P<0.01),补骨脂汤高、低剂量,均可明显提高NR2B、BDNF/TrkBmRNA表达(P<0.05).结论 补骨脂汤能明显改善血管性痴呆大鼠的空间记忆,其可能的机制是通过提高NR2B、BDNF/TrkBmRNA表达水平而发挥作用的.     

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission,oxidative stress and the ERK‐CREB‐BDNF signaling pathway

Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.     

铁筷子挥发油对慢性脑缺血致血管性认知功能障碍大鼠的作用及机制研究

目的 探究苗药铁筷子[腊梅Chimonanthus praecox及山腊梅C. nitens的干燥根]挥发油对慢性脑缺血（chronic cerebral hypoperfusion,CCH）致血管性认知功能障碍（vascular cognitive impairment,VCI）大鼠的作用及机制。方法 采用改良的双侧颈总动脉结扎（bilateral common carotid artery occlusion,BCCAO）法建立CCH模型,将造模成功大鼠随机分为模型组及铁筷子挥发油高、中、低剂量（80、40、20 mg/kg）组和丁苯酞（63 mg/kg）组,另设假手术组,给予相应药物干预28 d,采用水迷宫实验检测各组大鼠学习记忆能力;采用旷场实验、Y迷宫实验检测各组大鼠自主活动性和新奇事物探索能力;采用苏木素-伊红（HE）染色、Nissl染色、TUNEL染色观察各组大鼠大脑皮层及海马CA1区神经细胞结构变化、尼氏小体以及凋亡细胞数量变化;采用ELISA法检测各组大鼠血清中脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）水平;采用比色法检测各组大鼠海马组织中乙酰胆碱酯酶（acetylcholinesterase,AChE）和乙酰胆碱转移酶（cholineacetyltransferase,ChAT）的活性;采用Western blotting法检测各组大鼠海马组织中BDNF、酪氨酸激酶受体B（tyrosine kinase receptor B,TrkB）、磷酸化TrkB（phosphorylated TrkB,p-TrkB）、磷脂酰肌醇-3-激酶（phosphatidylin-ositol-3-kinase,PI3K）、蛋白激酶B（Akt）、p-Akt和半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3,Caspase-3）蛋白表达。结果 与模型组比较,铁筷子挥发油组大鼠逃避潜伏期缩短（P＜0.05、0.01）,穿越平台次数和跨格次数提高（P＜0.05、0.01）,在新异臂所待时间延长（P＜0.05）;神经细胞结构的变性得到改善,脑组织中尼氏小体的数量提高（P＜0.05）,细胞凋亡减少（P＜0.05）;血清中BDNF水平及海马组织中ChAT活性升高（P＜0.05、0.01）,海马组织中AChE活性降低（P＜0.05）;海马组织中BDNF、TrkB、p-TrkB、PI3K和p-Akt蛋白表达水平均显著升高（P＜0.05、0.01）,Caspase-3蛋白表达水平降低（P＜0.05）。结论 苗药铁筷子挥发油可以改善CCH致VCI大鼠认知功能障碍,其作用机制可能与激活BDNF/TrkB/PI3K/Akt信号通路有关。     

Effects of Ginsenoside Rg1 on Learning and Memory in a Reward‐directed Instrumental Conditioning Task in Chronic Restraint Stressed Rats

Ginsenoside Rg1 is one of the major active ingredients of Panax ginseng and has showed notable improving learning and memory effects in several behavioral tasks, such as water maze, shuttle‐box, and step‐through, based on avoidance. However, there was no report about the role of Rg1 on the performance of reward‐directed instrumental conditioning, which could reflect the adaptive capacity to ever‐changing environments. Thus, in this study, the reward devaluation test and conditional visual discrimination task were conducted to study the ameliorating effects of Rg1 on cognitive deficits, especially the loss of adaptation capacity in chronic restraint stress (CRS) rat model. Our results showed that rat subjected to CRS became insensitive to the changes in outcome value, and it significantly harmed the rat's performance in conditional visual discrimination task. Moreover, the levels of BDNF, TrkB, and Erk phosphorylation were decreased in the prefrontal cortex of CRS rats. However, these changes were effectively reversed by Rg1 (5 and 10 mg/kg, i.p.). Therefore, it demonstrated that Rg1 has a good ability to improve learning and memory and also ameliorate impaired adaptive capacity induced by CRS. This amelioration effect of Rg1 might be mediated partially by BDNF/TrkB/Erk pathway in prefrontal cortex. Copyright © 2016 John Wiley & Sons, Ltd.     

逍遥散抗抑郁作用的BDNF/CREB信号机制

目的:探讨逍遥散抗抑郁作用的BDNF/CREB信号机制。方法:采用小鼠慢性温和不可预知应激(CUMS)结合孤养抑郁模型,逍遥散水煎液30g/kg灌胃给药4周,测定小鼠体重、自主活动及糖水消耗量的变化以评价药物的抗抑郁效应。ELISA法测定血清BDNF水平,实时荧光定量聚合酶链式反应(real-time PCR)测定小鼠海马及皮质部位CREB、BDNF mRNA表达,Western-blot方法测定小鼠脑内ERK1/2及磷酸化ERK1/2(pERK1/2)的蛋白表达量。结果:与模型组比较,逍遥散30g/kg能提高模型小鼠体重、自主活动及糖水消耗量,并有提高模型动物血清BDNF含量的趋势;逍遥散30g/kg显著增加模型小鼠海马BDNF、CREB mR-NA及皮质BDNF mRNA的表达量,对模型动物海马部位pERK1/2的表达量有提高趋势。结论:逍遥散对CUMS结合孤养的小鼠抑郁模型具有抗抑郁效应,作用机制与干预BDNF/CREB信号途径的关键分子的表达与功能有关。     

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway

Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aβ_1–42. The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aβ_1–42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aβ_1–42 as assessed by the locomotor activity test, Y‐maze test, and Morris water maze test. Furthermore, the activities of superoxide dismutase and malondialdehyde in the hippocampus and cerebral cortex were elevated by KF administration. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with KF. In addition, we found KF could boost brain‐derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element‐binding (CREB) protein signal in the hippocampus. All results illustrated that KF could exert neuroprotective effects at least partly through alleviating oxidative stress and enhancing the BDNF/TrkB/CREB pathway in Aβ_1–42‐induced mice.     

ACUPUNCTURE STIMULATION IMPROVES MEMORY IMPAIRMENT INDUCED BY SCOPOLAMINE IN RATS

Objective: The purpose of this study was to examine whether acupuncture stimulation at the Baihui(GV20) improves memory defects caused by administration of scopolamine(SCO) to the rats.The effects of acupuncture stimulation at the GV20 on the cholinergic system as well as the expression of brain-derived neurotrophic factor(BDNF) and cAMP-response element-binding protein(CREB) in the hippocampus were also investigated.Methods: Male rats were administered with SCO(2 mg/kg, i.p.) once daily for 14 days.Acupuncture stimulation at GV20 was performed for 5 min before SCO injection.Results: Acupuncture stimulation at GV20 improved memory impairment as measured by the passive avoidance test(PAT) and reduced the escape latency for finding the platform in the Morris water maze(MWM) test.Acupuncture stimulation at the GV20 significantly alleviated memory-associated decreases in the expression levels of choline acetyltransferase(ChAT), BDNF and CREB proteins in the hippocampus.Additionally, acupuncture stimulation at the GV20 significantly restored the expression of choline transporter 1(CHT1), vesicular acetylcholine transporter(VAChT), BDNF and CREB mRNAs in the hippocampus.Conclusion: These results demonstrated that acupuncture stimulation at the GV20 has significant neuroprotective effects against neuronal impairment and memory dysfunction caused by SCO in rats.Thus, these findings suggested that acupuncture stimulation at the GV20 might be a useful therapy in various neurodegenerative diseases for the improvement of cognitive functioning via stimulating cholinergic enzyme activities and regulating BDNF and CREB expression in the brain.     

Rapid antidepressant‐like effect of Fructus Aurantii depends on cAMP‐response element binding protein/Brain‐derived neurotrophic facto by mediating synaptic transmission

Several studies reported the relative antidepressant effects of Fructus Aurantii (FRA) with repeated treatment, the rapid antidepressant effects of FRA and the underlying mechanisms remained unclear. We, therefore, examined the rapid antidepressant actions of FRA in behavioral tests in mice and tested the underlying molecular mechanisms. We found FRA, like ketamine, reversed the behavioral deficits both in lipopolysaccharide(LPS)‐induced and learned helplessness (LH) models at 1 day after a single administration. FRA was also capable of increasing the expressions of protein kinase A/cAMP‐response element‐binding protein/brain‐derived neurotrophic factor (PKA/CREB/BDNF) signaling in hippocampus. Consistent with ketamine, FRA up‐regulated the expressions of GABAergic receptor (GAD67) and glutamatergic receptor 1 (GluR1) in mouse hippocampus both exposed to LPS and LH. Moreover, synaptic proteins such as postsynaptic density‐95 (PSD95) and synapsin1 were also up‐regulated by a single dose of FRA both in LH and LPS models, like ketamine. Finally, metadoxine (an antagonist of CREB) inhibited the antidepressant effects of FRA in tail suspension test (TST) and forced swimming test (FST) in LPS‐induced mice, which also blocked the phosphorylation of CREB and the expressions of neurotransmitters and synaptic molecules. Therefore, FRA had rapid antidepressant effects, which depended on PKA/CREB/BDNF pathway, subsequently regulated the downstream synaptic transmission.     

调肝解毒方对慢性癫痫大鼠学习记忆及海马组织环磷酸腺苷反应元件结合蛋白表达的影响

目的观察调肝解毒方对慢性癫痫大鼠学习记忆与海马组织环磷酸腺苷反应元件结合蛋白(CREB)表达的影响。方法60只大鼠腹腔注射印防己毒素制作慢性癫痫模型后,随机分为模型组,调肝解毒方低剂量组、调肝解毒方高剂量组,丙戊酸钠组,每组15只,与正常组(15只)同期观察或治疗60天,以Morris水迷宫观察大鼠空间学习和记忆能力,应用RT-PCR方法检测大鼠海马组织CREBmRNA表达变化,免疫组织化学方法检测海马组织磷酸化的CREB水平变化。结果调肝解毒方低、高剂量组大鼠空间记忆能力高于模型组(P<0.01),海马组织CREBmRNA相对吸光度值增高,pCREB免疫阳性细胞的表达有不同程度增强,与模型组比较差异有显著性意义(P<0.05,P<0.01)。结论调肝解毒方可在一定程度上改善反复癫痫大鼠的学习记忆能力,可能与调节海马CREB表达有关。     

电针治疗抑郁模型大鼠快速起效海马区BDNF-TrkB机制研究

目的:探讨电针抗抑郁治疗快速起效的海马神经元保护和发生机制。方法:SD大鼠32只随机分为正常组、模型组、药物组(盐酸氟西汀)和电针组,每组8只。采用孤养和长期中等强度未预知应激制备应激大鼠抑郁症模型,运用免疫组化法观察治疗7天时各组大鼠在海马CA1、CA3、DG各区BDNF及TrkB阳性神经元的表达。结果:①抑郁症模型存在海马区BDNF、TrkB表达下降,表现为阳性神经元平均灰度值上升、目标总面积下降;②治疗第7天,电针组海马神经元的BDNF及受体TrkB平均灰度值下降,且显著低于药物组,尤以CA3区为甚(P<0.01);③治疗第7天,电针组海马神经元的BDNF及受体TrkB阳性神经元总面积均明显升高,且明显高于药物组,以在DG区较为显著(P<0.05)。结论:电针能提高抑郁模型大鼠海马锥体神经细胞的生存、促进神经元再生;电针抗抑郁快速起效与BDNF、TrkB表达的迅速增加有关。     

补肾方药对衰老大鼠海马学习记忆相关基因BDNF及其受体TrkB mRNA表达的影响

目的:观察补肾方药左归丸、右归丸对衰老大鼠海马学习记忆相关基因脑源性神经营养因子(BDNF)及其受体TrkB mRNA表达的影响,探讨老年大鼠学习记忆功能减退的部分分子机理,以及左归丸、右归丸的改善作用。方法:以自然衰老SD大鼠为动物模型,随机分设4组:青年对照组、老年对照组、老年左归丸组、老年右归丸组。采用原位杂交技术,观察各组大鼠大脑切片海马各分区(CA1、CA2、CA3、DG)BDNF、TrkB mRNA表达变化。结果:与青年对照组相比,老年对照组大鼠海马各分区的BDNF、TrkB mRNA表达均明显减弱(P<0.05),而左归丸、右归丸能不同程度地提高老年对照组大鼠海马DG、CA1、CA2、和CA3分区低下的BDNF、TrkB mRNA的表达。结论:老年大鼠的学习记忆功能退化,与学习记忆相关的基因BDNF、Trk B表达异常有关。而滋补肾阴方药左归丸、温补肾阳方药有归丸能通过提高BDNF、TrkB基因的表达,进而改善老年大鼠的学习记忆功能,延缓机体衰老。