柴胡-白芍对抑郁大鼠海马神经递质的影响

通过观察柴胡-白芍药对治疗抑郁模型大鼠海马中枢神经递质变化及BDNF和Trk B表达的情况,探讨其抗抑郁症的机理.采用HPLC法测定海马组织单胺类神经递质5-HT(5-羟色胺)、NE(去甲肾上腺素)、DA(多巴胺)的质量比.采用免疫组化法检测海马中BDNF(海马脑源性神经元)和Trk B(受体型酪氨酸蛋白激酶)阳性神经元面密度值的变化.结果表明,与模型组比较,柴胡白芍药对高、中剂量组海马单胺类神经递质5-HT,NE和DA质量比均显著增加,差异均有统计学意义(P0.05或P0.01);上调BDNF和Trk B阳性神经元面密度值(P0.05或P0.01).其作用机制可能是提高大鼠脑内海马组织和皮质组织NE、5-HT、DA质量比及上调BDNF(海马脑源性神经元)和Tr KB(受体型酪氨酸蛋白激酶)的表达.     

耳针对脑缺血后睡眠剥夺大鼠下丘脑单胺类神经递质和细胞因子IL-1β的影响

目的:通过观察耳针对脑缺血后睡眠剥夺大鼠下丘脑单胺类神经递质和细胞因子IL-1β的影响,探讨耳针治疗卒中后失眠的作用机制.方法:取SPF级Wistar雄性大鼠,用Zea Logna等报道的大脑中动脉栓线法(MCAO)制备大脑中动脉闭塞再灌注模型,模型成功后将动物随机分为对照组、模型组、安定组和耳针组4组,再对除对照组外的其他3组动物腹腔注射对氯苯丙氨酸(PCPA)造成脑缺血后睡眠剥夺大鼠模型,安定组每日腹腔注射安定,耳针组取耳穴神门(TF4)进行皮内针埋藏,均连续治疗7 d.采用酶联免疫吸附测定法(ELISA)检测下丘脑单胺类神经递质5-羟色胺(5-HT)、5-羟引哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)和白介素-1β(IL-1β)的含量.结果:与对照组相比模型组大鼠下丘脑5-HT、5-HIAA和IL-1β含量减低(P0.05),DA、NE含量显著升高(P0.01);与模型组相比安定组与耳针组大鼠下丘脑5-HT和IL-1β含量显著升高(P0.01),DA、NE含量显著降低(P0.01).结论:耳针治疗卒中后失眠可能通过提高机体下丘脑5-HT、5-HIAA及细胞因子IL-1β含量,降低NE和DA的含量以调节和改善睡眠.     

微透析电化学检测在线联用实时分析烟碱依赖大鼠伏隔核内单胺化合物的变化

为探讨烟碱依赖的形成机理,采用微透析和高效液相色谱-库仑阵列电化学检测器在线联用方法测定了大鼠伏隔核内多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）、高香草酸（HVA）、5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的含量变化.以1.5 μL/min灌流,每15 min收集1次透析液并自动注入梯度洗脱条件下的色谱进行检测.1.0 mg/kg烟碱暴露后,正常大鼠伏隔核内DA和5-HT的含量分别为基础水平的149%和134%,代谢产物DOPAC、HVA和5-HIAA的含量显著升高;烟碱依赖大鼠脑内5种单胺化合物的含量低于盐水对照组,1.0 mg/kg烟碱暴露后DA和5-HT的含量分别为基础水平的125%和119%,3.0 mg/kg烟碱暴露使DA和5-HT的释放增加至基础水平的147%和135%.结果表明,与正常大鼠相比,烟碱依赖发生后,更高剂量的烟碱方能激发同等水平的单胺神经递质释放及代谢变化特征.本研究为探讨烟碱依赖的形成机理提供了新的数据参考.     

红景天苷对运动疲劳大鼠神经递质影响研究

观察高山红景天苷对运动性疲劳大鼠中枢单胺类神经递质DA、5-HT、5-HIAA、NE质量比的影响,探讨其抗运动性疲劳的机制.将Wistar大鼠随机分成4组,每组10只,分别为阴性对照组(生理盐水);高山红景天苷低剂量组、中剂量组和高剂量组,建立中枢疲劳模型,分别灌胃给药,取大脑组织制备样本,检测神经递质DA、5-HT、...     

尼古丁剂量依赖性降低大鼠纹状体内多巴胺的释放

利用碳纤维电极在体(invivo)恒压伏安法检测大鼠纹状体(CPu)内由电刺激前脑内侧束(mfb)所引起的DA释放,探讨急性腹腔注射尼古丁对纹状体内多巴胺(DA)动态释放的影响.结果发现,尼古丁可导致CPu内的DA刺激-释放呈剂量依赖性降低,其中0.6mg/kg的尼古丁可明显降低DA的释放量,与生理盐水组相比差异显著.     

补充谷氨酰胺对大鼠跑台运动后血、脑多巴胺和去甲肾上腺素的影响

本研究旨在通过补充不同剂量的谷氨酰胺(Gln)，观察大鼠力竭性运动应激时血清和脑内去甲肾上腺素(NE)和多巴胺(DA)的反应性。40只大鼠随机分为4组，分别灌服大、小剂量Gln、淀粉溶液和水，共20天。第20天，补充Gln和补淀粉的大鼠进行力竭性跑台运动，并在运动后即刻处死；补水大鼠直接处死。测定血、脑Gln、NE、DA水平。结果显示，补充Gln大剂量 运动组第10天血清Gln、DA、NE及处死时脑组织DA显性高于补淀粉 运动组：补充Gln大剂量 运动组第10天血清Gln、处死时血清NE显性高于补充Gln小剂量 运动组；补淀粉 运动组第10天血清Gln、DA和NE均显性低于安静对照组大鼠，但处死时脑组织Gln显性高于安静对照组。提示，补充淀粉和Gln均可能影响血脑NE和DA含量；补充Gln可能提高大鼠力竭性运动应激后脑组织对DA升高的耐受，并有维持NE平衡的作用，提高大鼠对运动应激的反应能力和中枢的耐受能力，且大剂量补充Gln效果较好。     

热应激下脑内单胺类神经递质及其受体对运动性中枢疲劳影响的研究进展

乙酰胆碱(Ach)、去甲肾上腺素(NE)和5-羟色胺(5-HT)等神经递质参与下丘脑的体温调节,其受体亚型的不同也有不同的调节作用。在高温环境中,多巴胺(DA)、5-HT、NE伴随大脑和核心体温的升高而增加。提高5-HTR2活性会引起体温升高,而提高5-HTR1A活性的则会引起体温降低,DAR1、DAR2两者协同作用于体温的降低。单胺类神经递质含量改变及平衡的破坏是导致运动性中枢疲劳发生的因素之一。热应激条件下机体大脑和核心温度升高,脑内热储备过多,导致中枢疲劳的发生,提高DA、NE的活性可抑制高温介导的中枢疲劳,改善热应激下运动能力,但未能证明在高温环境下长时间运动5-HT介导疲劳的特殊作用。     

多巴胺与睡眠——觉醒

睡眠—觉醒是人类和某些动物的重要生理活,它的发生机制至今尚未完全澄清,但人们已认识到睡眠—觉醒的产生是一个复杂的过程,它涉及到脑内许多神经结构及多种神经活性物质(如:NE、Ach、DA、5—HT 及多肽类等)。其中 DA 及 DA 能神经系统参与睡眠—觉醒的调节作用日渐引起人们的关注。     

三环类药物及人参皂甙抗抑郁作用机制的研究

本研究采用大鼠强迫游泳实验法考察三环类药物及人参皂甙抗抑郁效果研究,对其脑内单胺类神经递质(去甲肾上腺素、多巴胺、5-羟色胺),用荧光分光光度法进行了定量测定,结果表明:高剂量丙米嗪和人参皂甙能降低脑内游离型去甲肾上腺素、多巴胺、5-羟色胺神经递质,从而使中枢神经系统突触部位结合型递质含量增高.推论三环类药物及人参皂甙抗抑郁作用机制可能与此效应有关.     

同步荧光-双波长法同时测定血浆中儿茶酚胺类神经递质

建立一种同步荧光法与双波长法结合起来同时测定血浆中肾上腺素(E)、去甲肾上腺素(NE)和多巴胺(DA)3种儿茶酚胺类神经递质的方法.对E,NE和DA 3种神经递质的衍生物分别进行同步荧光扫描,考察影响体系荧光强度的因素.△λ=70 nm时获得的同步荧光光谱图中,DA在385.0 nm处的荧光信号不受干扰,而且E和NE的相互干扰可通过双波长法消除.最佳实验条件:0.5 mol/L乙酸一乙酸钠为缓冲液(pH=6.5),E,NE和DA的加热时间分别为1,3和35 min.E,NE和DA线性范围分别为0～320,0～640μg/L和0～160μg/L,相关系数分别为0.999 5,0.999 8和0.999 3;最低检测限分别为0.20,0.97μg/L和0.73μg/L;血浆样品经酸性正丁醇和正庚烷进行处理.该法用于血浆中儿茶酚胺类神经递质的测定,结果令人满意.     

均匀磁场的研制及生物效应机制的探讨

研制了一种强度、频率及信号占空系数均可调节的生物医学研究用低频方波电压调制四阶均匀交变磁场 .并提出激发场生物效应的不可忽略性 ,以及非稳恒磁场与稳恒磁场生物医学效应不尽相同的原因     

基于TMAES对GrC神经元放电活动影响的仿真

经颅磁声电刺激（TMAES）是一种新型无创的脑神经调控技术,具有良好的应用前景.该技术利用静磁场和超声波共同作用所产生的磁声电效应,在神经组织中产生感应电流,进而对神经组织实施刺激.作者基于小脑颗粒细胞模型（GrC模型）,建立了突触连接GrC模型,对TMAES刺激下突触连接GrC模型的动作电位进行仿真,分析了动作电位的传播方向.在TMAES神经元的不同突触连接方式下,对比了兴奋性与抑制性对神经元放电的影响.通过改变抑制点的位置分析了抑制作用在TMAES下对神经元放电模式的影响.仿真结果显示,经颅磁声电刺激对GrC模型神经元放电节律具有重要影响.实现了两个神经元突触连接模型在TMAES下的仿真,对进一步发掘和研究神经元的传导及连接模式具有重要意义.     

手针和电针足三里穴持续性效应的功能磁共振成像研究

通过采集的静息态脑功能磁共振成像数据和并对其进行分析,分别探索传统手针和电针足三里穴的人脑持续性效应的中枢神经系统活动.选择12例(6男,6女,23～27岁)无针刺经历的、右利手健康成年志愿者,分成手针组(12例)和电针组(12例).手针刺激(2 Hz)和电针刺激(2 Hz,连续方波,电流强度0.5～1.4 mA)实验中,针刺刺激分别以2 Hz的频率对足三里进行2 min的双向捻转,采集针刺刺激前后静息态的数据进行预处理并对其进行统计分析.统计结果显示手针和电针针刺足三里后引起了不同的持续性效应,包括中脑和基底神经节在内的参与与镇痛有关的神经递质释放的脑区结构,在针刺刺激后阶段呈现出了持续性的活动.两种针刺模态下不同的脑区响应模式表明两者可能在经络传输通道和神经递质系统的活动存在差异.     

Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes

A variety of evidence indicates that calcium-dependent protein phosphorylation modulates the release of neurotransmitter from nerve terminals. For instance, the injection of rat calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-dependent PK II) into the preterminal digit of the squid giant synapse leads to an increase in the release of a so-far unidentified neurotransmitter induced by presynaptic depolarization. But until now, it has not been demonstrated that Ca2+/CaM-dependent PK II can also regulate neurotransmitter release in the vertebrate nervous system. Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline. We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release. These results support the hypothesis that activation of Ca2+/CaM-dependent PK II in the nerve terminal removes a constraint on neurotransmitter release.     

Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites

Information in neurons flows from synapses, through the dendrites and cell body (soma), and, finally, along the axon as spikes of electrical activity that will ultimately release neurotransmitters from the nerve terminals. However, the dendrites of many neurons also have a secretory role, transmitting information back to afferent nerve terminals. In some central nervous system neurons, spikes that originate at the soma can travel along dendrites as well as axons, and may thus elicit secretion from both compartments. Here, we show that in hypothalamic oxytocin neurons, agents that mobilize intracellular Ca(2+) induce oxytocin release from dendrites without increasing the electrical activity of the cell body, and without inducing secretion from the nerve terminals. Conversely, electrical activity in the cell bodies can cause the secretion of oxytocin from nerve terminals with little or no release from the dendrites. Finally, mobilization of intracellular Ca(2+) can also prime the releasable pool of oxytocin in the dendrites. This priming action makes dendritic oxytocin available for release in response to subsequent spike activity. Priming persists for a prolonged period, changing the nature of interactions between oxytocin neurons and their neighbours.     

Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonists in hippocampus

Since the initial observations in the 1950s a large number of neurotransmitters and hormones have been shown to influence phosphatidylinositol (PI) metabolism in brain and peripheral ganglia (see ref. 3 for review). This has led to the suggestion that PI is part of an intracellular second messenger system for some types of diffusible chemical factors. Consistent with this are recent reports that one of the products of PI turnover (diacylglycerol) stimulates the Ca-dependent phospholipid-dependent protein kinase (kinase C) while a second (inositol trisphosphate) causes the release of calcium from intracellular stores. Thus it is possible that at least some brain neurotransmitters utilize the PI system to produce functional effects that are in addition to and which outlast the very brief physiological responses they elicit. Although it had been anticipated that another class of receptors might inhibit receptor-mediated stimulation of PI breakdown, no clear examples of such effects have been described. We now report that acidic amino acids, which are that acidic amino acids, which are thought to be excitatory neurotransmitters at the majority of brain synapses, strongly inhibit the stimulation of PI metabolism elicited by carbachol, histamine, or by potassium-induced depolarization, without changing the response to noradrenaline. As well as indicating a novel function for the excitatory amino acids, these results suggest that the central nervous system possesses cell-cell interactions of a previously unsuspected type.     

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels, which are densely localized in nerve terminals. Because neurotransmitter release is proportional to the fourth power of calcium concentration, regulation of its entry can profoundly influence neurotransmission. N- and P/Q-type calcium channels are inhibited by G proteins, and recent evidence indicates feedback regulation of P/Q-type channels by calcium. Although calcium-dependent inactivation of L-type channels is well documented, little is known about how calcium modulates P/Q-type channels. Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the alpha1A subunit of P/Q-type channels. In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current. These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain. Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity.     

钙通道抑制剂对川百合花粉萌发的影响

细胞内钙离子在花粉萌发过程中发挥重要作用,钙离子如何被植物花粉细胞所吸收是植物生殖生理研究的热点问题．对一些常用的钙通道抑制剂对川百合花粉萌发和花粉管伸长生长的影响进行了研究．结果表明,萌发中的花粉需要从外界吸收大量钙离子,电压依赖型钙通道的有机抑制剂(异搏定、尼群地平、地而流卓)和3价无机离子(镧、铝、钆)可以明显抑制花粉萌发,电压依赖型通道很可能是细胞外钙离子进入萌发花粉的重要途径．     

Glutamate spillover suppresses inhibition by activating presynaptic mGluRs

Metabotropic glutamate receptors (mGluRs) found on synaptic terminals throughout the brain are thought to be important in modulating neurotransmission. Activation of mGluRs by synaptically released glutamate depresses glutamate release from excitatory terminals but the physiological role of mGluRs on inhibitory terminals is unclear. We have investigated activation of mGluRs on inhibitory terminals within the cerebellar glomerulus, a structure in which GABA (gamma-aminobutyric acid)-releasing inhibitory terminals and glutamatergic excitatory terminals are in close apposition and make axo-dendritic synapses onto granule cells. Here we show that 'spillover' of glutamate, which is released from excitatory mossy fibres, inhibits GABA release from Golgi cell terminals by activating presynaptic mGluRs under physiological conditions. The magnitude of the depression of the inhibitory postsynaptic current is dependent on the frequency of mossy fibre stimulation, reaching 50% at 100 Hz. Furthermore, the duration of inhibitory postsynaptic current depression mirrors the time course of mossy fibre activity. Our results establish that mGluRs on inhibitory interneuron axons sense the activity of neighbouring excitatory synapses. This heterosynaptic mechanism is likely to boost the efficacy of active excitatory fibres by locally reducing the level of inhibition.     

Opioids block long-term potentiation of inhibitory synapses

Excitatory brain synapses are strengthened or weakened in response to specific patterns of synaptic activation, and these changes in synaptic strength are thought to underlie persistent pathologies such as drug addiction, as well as learning. In contrast, there are few examples of synaptic plasticity of inhibitory GABA (gamma-aminobutyric acid)-releasing synapses. Here we report long-term potentiation of GABA(A)-mediated synaptic transmission (LTP(GABA)) onto dopamine neurons of the rat brain ventral tegmental area, a region required for the development of drug addiction. This novel form of LTP is heterosynaptic, requiring postsynaptic NMDA (N-methyl-d-aspartate) receptor activation at glutamate synapses, but resulting from increased GABA release at neighbouring inhibitory nerve terminals. NMDA receptor activation produces nitric oxide, a retrograde signal released from the postsynaptic dopamine neuron. Nitric oxide initiates LTP(GABA) by activating guanylate cyclase in GABA-releasing nerve terminals. Exposure to morphine both in vitro and in vivo prevents LTP(GABA). Whereas brief treatment with morphine in vitro blocks LTP(GABA) by inhibiting presynaptic glutamate release, in vivo exposure to morphine persistently interrupts signalling from nitric oxide to guanylate cyclase. These neuroadaptations to opioid drugs might contribute to early stages of addiction, and may potentially be exploited therapeutically using drugs targeting GABA(A) receptors.