人参总皂苷对大鼠海马齿状回突触传递活动的影响

目的：研究人参总皂苷对麻醉大鼠海马齿状回(DG)突触传递活动的影响。方法：采用在体记录LTP的电生理学方法,给予不同剂量人参总皂苷(100,50,25 mg.kg^-1,ip)观察其对海马DG基础突触传递活动和LTP的影响。 结果：给予人参总皂苷10 min后可剂量依赖性增强大鼠海马DG基础突触传递活动; 在给予高频刺激(HFS)诱导出LTP后30 min,再ip上述剂量人参总皂苷,可使已形成的LTP在ip人参总皂苷后持续增强。结论：人参总皂苷ip可剂量依赖性增强海马DG基础突触传递活动和HFS所诱导的LTP。     

围生期双酚A暴露对雄性子代大鼠海马CA1区神经元形态及突触可塑性的影响

目的研究围生期双酚A(BPA)暴露对♂子代大鼠海马CA1区神经元形态及突触可塑性的影响。方法对SD大鼠的母鼠从妊娠d11直至产后7d每日分别皮下注射3种剂量的BPA(10、100、1000μg·kg-1作为低、中、高剂量组),同时注射食用色拉油设立对照组。统计各组母鼠产仔数,并观察母鼠吃仔情况。在♂子鼠出生21d后,取脑组织切片,进行HE染色;或用电生理学方法检测BPA暴露对海马CA1区LTP及LTD诱导率的影响。结果高剂量BPA组母鼠吃仔率明显高于对照组(P<0.01);HE染色结果显示,高剂量BPA组♂子鼠海马CA1区锥体细胞发生核固缩变性,异常锥体神经元数量明显增多(P<0.05);低剂量BPA组♂子鼠海马脑片CA1区LTP诱导成功率与对照组相比明显降低(P<0.05),而LTD诱导成功率则明显升高(P<0.05)。结论围生期BPA暴露可以损伤♂子代大鼠海马CA1区神经元形态及突触传递可塑性。     

人参皂甙Rg1对大鼠神经传递作用的机制研究

目的研究NMDA受体及电压依赖性钙通道在人参皂苷Rg1对麻醉大鼠海马神经传递的作用。方法采用胞外记录的方法观测在体麻醉大鼠齿状回群峰电位的幅度,观察AP5和尼莫地平对神经传递的影响。结果 AP5和尼莫地平对麻醉大鼠海马基础突触传递水平没有影响,但APV抑制了Rg1海马齿状回突触传递长时程增强的诱导,尼莫地平对于Rg1诱导的长时程增强没有影响。结论 Rg1所诱导的神经传递长时程增强为NMDA受体依赖性的,非VDCC依赖性。     

三七总皂苷对海马CA1区长时程增强效应的影响

三七总皂苷(Panax notoginseng saponins，PNS)是从传统中药三七的根中提取的主要有效成分， 具有改善血液循环、 耐缺氧、 改善记忆力、 抗衰老等多方面的生理活性。本研究采用“盲法”全细胞膜片钳技术观察PNS对大鼠海马CA1区锥体神经元长时程增强效应(LTP)的影响， 以分析其增强学习记忆功能的神经电生理机制。以断头法分离Wistar大鼠(3～4周)海马半脑， 用切片机切出400 μm厚度的海马脑片， 以全细胞电压钳制方式记录CA1区锥体细胞的兴奋性突触后电流(EPSCs)， 给予高频刺激HFS(100 Hz)诱导LTP， 分析PNS对大鼠海马CA1区EPSCs和LTP的影响。结果表明， PNS(0.1～0.4 g·L^-1)能显著抑制EPSCs(P<0.05)， 且对海马CA1区LTP无易化作用； 但PNS(0.04～0.05 g·L^-1)不影响CA1区的EPSCs基础突触传递(P>0.05)， 却可以增强HFS诱发的LTP(P<0.05)。上述结果提示， PNS(0.04～0.05 g·L^-1)能易化海马CA1区锥体神经元的长时程增强效应，该作用应是其增进学习记忆力的神经电生理机制。     

一氧化氮介导麻醉大鼠人参皂苷Rg1诱发长时程增强

目的：研究人参皂苷Rg1对麻醉大鼠突触传递效能的影响及作用机制。方法：应用细胞外微电极录技术,记录麻醉大鼠海马齿状回颗粒细胞群体峰电位（PS）。结果：Rg1(10,100nmol/L)提高麻醉大鼠的基础突触传递,诱导海马齿状回突触传递长时程增强（LTP）,并提高高频刺激所诱导的LTP。选择性NOS抑制剂7－硝基吲唑（7－NI,5nmol)侧脑室注射可明显抑制Rg1所诱导的齿状回LTP,对基础突触传递无明显影响。L－Arg(250mg/kg,ip)可拮抗 7－NI对Rg1诱导LTP的抑制作用（P＜0．05）。结论：Rg1显著促进麻醉大鼠的突触传递效能,由神经元型NOS（nNOS）所产生的NO参与了Rg1对齿状回LTP的诱导过程。     

当归芍药散活性部位JD-30对淀粉样β蛋白片段25-35抑制大鼠海马脑片CA1区长时程增强的改善作用

目的研究当归芍药散改善学习记忆能力的物质基础和作用机理。方法采用细胞外微电极记录技术,记录大鼠海马脑片CA1区群峰电位(PS)幅值和高频刺激诱发LTP后PS的增幅。结果用含当归芍药散活性部位JD-30(25,50和100mg.L-1)的人工脑脊液灌流大鼠海马脑片,其CA1区的PS幅值无明显变化。用相同浓度的JD-30孵育海马脑片90min以上并持续灌流,其CA1区高频刺激后的PS增幅与空白对照组相比无明显差异。而用Aβ25-35200nmo.lL-1处理的海马脑片CA1区高频刺激后的PS增幅受到明显抑制;若同时给予Aβ25-35和上述浓度的JD-30处理海马脑片,CA1区高频刺激后的PS增幅较Aβ25-35组升高,其中JD-30100mg.L-1组的PS增幅达到正常对照组水平。提示JD-30对正常海马脑片CA1区的基础突触传递和LTP没有影响,但可改善Aβ25-35所抑制的LTP。结论JD-30可改善神经突触可塑性,拮抗Aβ对LTP的抑制作用可能是其益智机制之一。     

氯胺酮对神经病理性痛大鼠海马CA1区突触长时程增强的影响

目的:探讨氯胺酮对神经病理性痛大鼠海马CA1区突触长时程增强(LTP)的影响。方法:成年雄性Wistar大鼠18只,体重190~220 g,随机分为3组(n=6):神经病理性痛模型组、假手术组、氯胺酮组。采用结扎L4,5左侧脊神经的方法制备大鼠神经病理性痛模型。于模型制备后1周、2周和3周观察大鼠痛行为学及足部形态;于模型制备前、后1周、2周和3周时测定痛阈;于最后一次痛阈测定结束后3 d记录海马CA1区兴奋性突触后电位(EPSP),以高频刺激(HFS)诱发LTP,氯胺酮组HFS前20 min经腹腔注射25 mg/kg。结果:与假手术组比较,模型组和氯胺酮组各时点痛阈降低;与模型组相比,氯胺酮组LTP程度减弱(P<0.01)。结论:氯胺酮可抑制神经病理性痛对大鼠海马CA1区突触LTP的易化作用。     

锂对大鼠海马齿状回区神经元突触可塑性的影响(英文)

目的　从齿状回长时程增强效应 (LTP)方面研究锂的治疗作用机理。方法　细胞外记录离体海马脑片神经元兴奋性突触后电位 (EPSP)。结果锂可逆地增强EPSP的幅度。高频刺激 (10 0Hz ,1s)对照组大鼠海马穿通纤维 ,在海马齿状回 (DG)区记录的EPSP幅度会持续增高 ,可以诱导出明显的突触后LTP。若用 10mmol·L- 1锂处理大鼠海马脑片 ,则诱导的LTP幅度明显降低 ,但低浓度锂 (2 ,6mmol·L- 1)不影响LTP的幅度 ;10mmol·L- 1锂明显抑制海马脑片DG区的脉冲间隔 (IPI)为 5 0ms的双脉冲易化效应 (PPF) ,而低浓度锂 (2 ,6mmol·L- 1)处理则不影响PPF(IPI,5 0ms) ;在不同的细胞外钙浓度下 ,用 10mmol·L- 1锂处理过的海马脑片PPF受到的抑制程度不同。结论　锂可能通过突触前的机理来抑制海马DG区LTP的幅度 ,这种抑制效应与锂的临床治疗狂躁症及其副作用之间的关系尚需进一步的研究。     

石杉碱甲对大鼠海马脑片CA1神经元θ节律及长时程增强的影响

目的:研究石杉碱甲(HupA)对大鼠海马脑片CA1锥体神经元θ节律、长时程增强的影响,以分析其增强学习记忆功能的神经细胞电生理机制。方法:应用大鼠海马脑片神经元细胞内记录技术,观察石杉碱甲对大鼠海马脑片的CA1锥体神经元θ节律、长时程增强的影响。结果:(1)未用药组出现膜电位振荡前后4～10Hz(θ节律)功率分量之和无显著性差异,但在HupA(1μmol·L-1)灌流15min后出现膜电位振荡,与用药前没有膜电位振荡的4～10Hz功率分量之和配对t检验比较有显著差异(n=3,P<0.005)。(2)在LTP期间,对照组EPSP幅度在强直刺激后30min显著性的升高(P<0.05),而HupA组在强直刺激后15min即出现显著性升高(P<0.01)。结论:HupA可增加大海马锥体神经元在θ频率范围内的功率分量,并易化LTP的诱发,这可能是其增强学习记忆功能的细胞电生理机制之一。     

人参皂甙Rg1对自由活动大鼠突触可塑性的影响及其作用机制

目的:研究人参皂甙Rg1对自由活动大鼠突触功能可塑性的影响及作用机制。方法：应用细胞外微电极记录技术,大鼠埋植电极后d6予以Rg1(10,30mg/kg,ip)12d,记录（直至停药后d3)其齿状回群体峰电位（PS）。大鼠给予Rg1(10,30mg/kg,ip)12d,据Timm染色法观察海马CA3区苔藓纤维出芽情况.吧免疫组化技术检测齿状回颗粒细胞层GAP－43表达水平。结果：1）Rg1可显著降低诱发PS的阈值,提高清醒自由活动大鼠的突触传递效能,诱导LTP形成,停药3d后,LTP仍可维持。2）Rg1组大鼠齿状回颗粒细胞层及齿状回门区GAP－43表达显著增加。3）Timm染色显示海马CA3区苔藓纤维出芽增加。结论：Rg1可使自由活动大鼠PP－DG突触传递效能发生吧LTP为主的可塑性变化,其机制为齿状回颗粒细胞GAP－43表达增加,其投射靶区海马CA3苔藓纤维明显出芽增加,这呈正反馈性增强了突触传递效能。     

Galantamine rescues lead-impaired synaptic plasticity in rat dentate gyrus

Chronic lead exposure causes a variety of impairments in learning and memory and cognitive function. Synaptic plasticity in hippocampus is an extensively studied cellular model of learning and memory, which includes long-term potentiation (LTP) and long-term depression (LTD) in two forms. Depotentiation (DP) is another form of synaptic plasticity. Previous studies show that chronic lead exposure can damage the induction of LTP/LTD in hippocampal CA1 and dentate gyrus (DG) areas. In the present study, we investigated the repair and protection on lead-caused synaptic plasticity impairment by galantamine, using field potential recording on chronic lead exposure rats. The results showed that chronic lead exposure impaired LTP/DP induction in DG area of the hippocampus, and galantamine caused a significant increase on the amplitudes of LTP/DP of lead-exposed rats, but only a small increase in non-exposed group. These results suggest that galantamine could reverse the lead-induced impairments of synaptic plasticity in rats and might be an effective medicine to cure the cognitive deficits induced by lead.     

白藜芦醇对大鼠海马CA1区诱发癫痫样放电的影响

目的观察不同浓度白藜芦醇(resveratrol,Res)对癫痫大鼠海马CA1区场电位的影响,为临床研发抗癫痫新药提供理论依据。方法正常大鼠海马脑片灌流γ-氨基丁酸受体拮抗剂bicuculline引起癫痫样活动以及在正常大鼠右侧海马CA3区注射海人藻酸(KA)建立颞叶癫痫(TLE)大鼠模型,应用离体脑片细胞外场电位记录,刺激辐射层Schaffer侧支通路,在海马CA1区锥体细胞层记录群峰电位(PS)的变化。结果正常大鼠海马脑片CA1区锥体细胞记录到的场电位为单个PS,分别灌流含有低、中和高剂量(分别为5、15和50μmol.L-1)Res的ACSF,PS幅度均无明显变化(n=8,P>0.05)。灌流bicuculline(30μmol.L-1)后,记录到的场电位为多个PS的痫样电位,在此基础上灌流低和中剂量的Res,PS幅度和数目没有明显改变(n=8,P>0.05);而灌流高剂量的Res,前4个PS幅度均有明显降低(n=8,P<0.01),PS数目也有明显减少(n=8,P<0.01)。在TLE模型大鼠海马脑片上记录到的场电位也为多个PS的痫样电位,灌流低和中剂量的Res,PS幅度和数目没有明显改变(n=6,P>0.05);灌流高剂量Res,前4个PS幅度均有明显降低(n=6,P<0.01),PS数目也有明显减少(n=6,P<0.01)。结论高剂量的Res能部分抑制大鼠海马CA1区诱发癫痫样放电活动。     

Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats

Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.     

三七总皂苷主要成分对人肝微粒体CYP3A4酶的抑制作用研究

目的：研究三七总皂苷主要成分人参皂苷Rg1、人参皂苷Rb1和三七皂苷R1对人肝微粒体CYP3A4酶的体外抑制作用.方法：采用人肝微粒体体外孵育法,在孵育体系中分别加入不同浓度的人参皂苷Rg1、人参皂苷Rb1和三七皂苷R1与探针底物睾酮共孵育,用LC-MS /MS 法测定代谢产物6β-羟基睾酮的生成量反映CYP3A4酶活性的影响.结果：人参皂苷Rg1在2～1 000 μmol·L-1的测试浓度范围内对CYP3A4未见剂量相关的抑制作用;人参皂苷Rb1在2～200 μmol·L-1的测试浓度范围内对CYP3A4未见剂量相关的抑制作用,在1 000 μmol·L-1的测试浓度下对CYP3A4具有轻微抑制作用;三七皂苷R1在2～1 000 μmol·L-1的测试浓度范围内对CYP3A4的IC50为126 μmol·L-1（＞100 μmol·L-1）.结论：三七总皂苷3个主要有效成分单体对CYP3A4酶的体外抑制作用不同,人参皂苷Rg1无抑制作用,人参皂苷Rb1高浓度下有轻微抑制作用,三七皂苷R1有弱抑制作用,三七总皂苷制剂与CYP3A4酶代谢相关的药物之间产生相互作用的可能性低.     

Age-related impairment of long-term depression in area CA1 and dentate gyrus of rat hippocampus following developmental lead exposure in vitro

Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term depression (LTD) has been reported in area CA1 and dentate gyrus (DG) of rat hippocampus following chronic lead exposure. The present study was carried out to investigate age-related alterations of LTD in area CA1 and DG of rat hippocampus following developmental lead exposure in vitro. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking 0.2% lead acetate solution. Field excitatory postsynaptic potentials (EPSPs) were recorded in hippocampal slices at various postnatal ages: postnatal day (PND) 17-23, 27-33, and 57-63. Following low-frequency stimulation (LFS, 900 pulses/1 Hz), the average magnitude of LTD is age related. In the controls, LTD magnitude in area CA1 decreased with age, whereas in DG it increased with age. In the lead-exposed groups, the magnitude of LTD declined during development in both area CA1 and DG. The differences of LTD magnitude between the control and lead-exposed rats were 27.26 +/- 9.15% (PND 17-23), 21.59 +/- 12.93% (PND 27-33), and 16.96 +/- 9.33% (PND 57-63) in area CA1, and were 6.95 +/- 9.26%, 17.60 +/- 3.91%, and 33.63 +/- 10.47% in DG, respectively. These results demonstrated that the lead-induced impairment of LTD magnitude was an age-related decline in area CA1 and an age-related increase in area DG of rat hippocampus. Published by Elsevier Science Inc.     

烟碱诱导的海马脑片CA_1区长时程增强呈钙离子依赖性(英文)

目的:观察钙离子在烟碱诱导的大鼠海马脑片CA_1区长时程增强中的作用。方法:细胞外记录离体海马脑片CA_1区锥体细胞层群体峰电位。结果:至少烟碱1μmol·L~(-1)可诱导海马CA_1区长时程增强形成。移去脑脊液中的钙离子,烟碱不能诱导CA_1区长时程增强形成。硝苯地平1与10μmol·L~(-1)部分抑制而Tharpsigargin 1与10μmol·L~(-1)完全抑制烟碱诱导的长时程增强形成。结论:烟碱诱导的海马CA_1区长时程增强呈钙离子依赖性,胞外钙内流和胞内钙释放都参与了长时程增强形成。     

Effects of sodium valproate on synaptic plasticity in the CA1 region of rat hippocampus.

Sodium valproate (VPA) is currently one of the major anticonvulsant drug in clinical use and has a wide spectrum of antiepileptic activity. Previous studies have reported that VPA impairs long-term potentiation (LTP). In the present study, we used two forms of synaptic plasticity, LTP and long-term depression (LTD) of field excitatory postsynaptic potential (fEPSP) to investigate the effects of VPA on synaptic plasticity in rat hippocampal slices. Paired-pulse facilitation (PPF) and field EPSP were recorded in the CA1 area of hippocampal slices exposed to VPA. The results showed that: (1) three different concentrations of VPA (0.6, 1 and 5 mM) all induced a significant impairment of PPF at 20-150 ms inter-pulse intervals (IPI) (P<0.05). (2) acute VPA exposure (0.6 mM) inhibited the induction of LTP (Control: 171 +/- 20%, n=8; VPA-exposed: 117 +/- 16%, n=9, P<0.01) and LTD (Control: 86 +/- 13%, n=8; VPA-exposed: 98 +/- 8%, n=10, P<0.01); and (3) GABA(A) receptor antagonist picrotoxin (PTX) (10 microM) reversed VPA-induced deficits of LTP (VPA-exposed: 117 +/- 16%, n=9; VPA-exposed+PTX: 153 +/- 20%, n=8, P<0.01). However, PTX had no significant effect on impairment of LTD (VPA-exposed: 98 +/- 8%, n=10; VPA-exposed+PTX: 97 +/- 3%, n=8, P>0.05). These results suggested that VPA impaired LTP and LTD. Furthermore, VPA-induced impairment of LTP could be correlated with the enhancement of inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA) receptor.     

Age-related morphological impairments in the rat hippocampus following developmental lead exposure: an MRI, LM and EM study

Lead is one of the most common neurotoxic metals present in our environment. Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Functional and morphological impairment of the rat brain has also been reported in the hippocampus (Hi) following developmental lead exposure. The present study was carried out to further investigate age-related morphological impairments in the rat Hi following developmental lead exposure with three methods: (1) magnetic resonance imaging (MRI); (2) light microscopy (LM); and (3) electron microscopy (EM) techniques. Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams drinking a 0.2% lead acetate solution. Age-related morphological alternations were investigated in the Hi of lead-exposed rats at various postnatal ages: postnatal day (PND) 17, 30 and 90. The MRI signal intensities (SIs) in the left, right, superior and inferior hippocampal regions of control and lead-exposed rats were analyzed. Compared with controls, the SIs of the four hippocampal regions of interest were significantly increased in lead-exposed rats at PND 17, 30 and 90. Moreover, the lead-induced impairment of the Hi showed an age-related decline and a specific topographical pattern. The impairment of inferior hippocampal regions was more severe than that of superior regions in lead-exposed rats at PND 17 and 30, while no significant difference of SIs was observed between left and right hippocampal regions in the three age groups, and between superior and inferior regions in the PND 90 lead-exposed rats. The LM observations indicated that the morphological injury of hippocampal neurons in lead-exposed rats was also age-related. The EM observations revealed that the endoplasmic reticular, Golgi complex and mitochondria of hippocampal CA1 and dentate gyrus neurons in lead-exposed rats were damaged. These results demonstrate that lead-induced morphological impairments of the rat Hi follow a specific age- and site-related pattern.     

In vivo sodium salicylate causes tolerance to acute morphine exposure and alters the ability of high frequency stimulation to induce long-term potentiation in hippocampus area CA1

Effects of morphine on synaptic transmission and plasticity in the hippocampus area CA1 following in vivo sodium salicylate and the potential molecular mechanism were investigated. Population spikes (PS) were recorded from stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from control and sodium salicylate injected rats. To induce long term potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine increased baseline PS amplitude in control slices but not in slices taken from sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate treated rats as compared to control ones. Following LTP induction, the mRNA of NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats were more than those of control ones. After long-term exposure to in vitro morphine, high frequency stimulation (HFS) decreased NR2A mRNA level significantly in sodium salicylate treated slices. It is concluded that in vivo sodium salicylate causes tolerance to excitatory effect of morphine and changes the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These changes in synaptic response may be due to alterations in NR2A and PP1 expression.