Dogma and dreams: experimental lessons for epilepsy mechanism chasers

Epilepsy mechanism chasers face one major difficulty. Since we don’t know how the normal brain works, we can’t start to understand how the diseased brain fails. Most of today’s hypotheses are based on what we think about ‘normal’ brain function, which may lead to misconceptions, as will be developed here. Furthermore, since there are many different types of epilepsies, some mechanisms may only be relevant to some epilepsies. Here, I shall focus on temporal lobe epilepsy (TLE) the most common form of partial epilepsy in adults. TLE is often drug resistant, as are 30–40% of all forms of epilepsies. The failure of drug-treatments most likely reflects our lack of knowledge of the underlying mechanisms.Received 10 January 2005; received after revision 3 March 2005; accepted 23 March 2005     

Genetic control of hippocampal cholinergic and dynorphinergic mechanisms regulating novelty-induced exploratory behavior in house mice

Summary Neurobehavioral genetics endeavors to trace the pathways from genetic and eenvironmental determinants to neuroanatomical and neurophysiological systems and, thence, to behavior. Exploiting genetic variation as a tool, the behavioral sequelae of manipulating these neuronal systems by drugs and antisera are analyzed. Apart from research in rats, this paper deals mainly with the genetically-influenced regulation in mice of exploratory behaviors that are adaptive in novel surroundings and are hippocampally-mediated. Special attention is paid to neuropeptidergic, GABAergic, and cholinergic synaptic functions in the mouse hippocampus.The behaviorally different inbred mouse strains C57BL/6 and DBA/2 show opposite reactions (reductions and increases, respectively, in exploration rates) to peripheral and intrahippocampal injections with agents that interfere with peptidergic, cholinergic, and GABAergic neurotransmission. These findings can be explained by an interdependent over-release of opioids, arrested GABA release, and excess acetylcholine in the hippocampal neuronal network of DBA/2 mice, as compared to C57BL/6 mice where these systems are functionally well balanced. Very similar results have been obtained with the lines SRH and SRL, derived from C57BL/6 and DBA/2, and genetically selected for rearing behavior. Most probably, the opioids act to disinhibit exploratory responses. An additional genetic approach is mentioned, in which four inbred mouse strains and one derived heterogeneous stock are used for estimating genetic correlations between structural properties of the hippocampal mossy fibers and levels of hippocampal dynorphin B, on the one hand, and frequencies of exploratory responses to environmental novelty, on the other.     

家兔海马的细胞构筑和纤维构筑

用七只家兔灌注后取背海马并沿其长轴作横切片,分别进行尼氏法、Weil法、Golgi改良法及Golgi—Деинека镀银法处理,在光学显微镜下观察家兔齿状回的结构、海马的层次、细胞类型及大小、海马中各地区的差异和海马内部进行相互连系的纤维.     

Effects of calcineurin on LTP of rats in vivo

Calcineurin (CN) is thought to play a role in the synaptic plastivity and long-term potentiation (LTP) in the hippocampus. Based on two LTP models in vivo, a specific inhibitor cyclosporin A (CsA) of CN was observed, which affected LTP in the hippocampal dentate gyrus of the rats. The results indicated that CsA blocked LTP induced by high frequency stimulation (HFS) partly, but it had no effect on the decrease of the onset and peak latency of population spikes (PS) except that it reduced the increase of the amplitude after HFS. On the other hand, CsA blocked LTP induced by ginsenosides (GSS) completely. It suppressed the GSS-enhanced amplitude of PS reversibly and blocked the decrease of the peak latency of PS induced by the GSS. These results suggest that the postsynaptic CN plays a role in the induction of LTP in the hippocampus of the rats.     

大鼠脑损伤海马神经干细胞bFGF表达及三七总皂苷的作用研究

目的探讨脑损伤对神经干细胞bFGF阳性细胞表达的影响及三七总皂苷的作用。方法通过免疫细胞化学的方法检测脑损伤后以及给予三七总皂苷后新生大鼠海马神经干细胞bFGF阳性细胞的表达。结果三七总皂苷可促进缺血再灌注组的bFGF阳性细胞的数目明显增多。缺血组1h、2h的bFGF阳细胞计数均多于正常组;模型组6h后阳性细胞计数开始低于正常组,具有统计学意义。24h给药组的bFGF阳性细胞的面密度和光密度均高于模型组,有显著性差异伙0.001）,具有统计学意义。结论体外模拟脑缺血在一定时间内能引起海马神经干细胞内的bFGF水平上调,三七总皂苷对bFGF水平的上调具有促进作用。     

谷氨酸、褪黑素导致海马脑薄片诱发群体峰电位的变化过程研究

在大鼠海马脑薄片上电刺激海马Schaffer侧支纤维 ,胞外记录CA1区锥体细胞层诱发群体峰电位 (PopulationSpike ,PS) ,观察灌流谷氨酸 (Glu)和褪黑素 (MEL) 40min ,人工脑脊液冲洗30min对PS的影响 ,结果显示 :不同浓度 ( 1 .0、1 .2 5、2 .5和 5.0mmol/L)的Glu作用下 ,70min末PS值百分比分别为 1 560 .5%、1 50 .7%、1 3.1 %、4.1 % ;并且Glu浓度高时 ( 2 .5或 5.0mmol/L) ,恢复期末增加刺激强度均不能使PS值升高 .不同浓度MEL( 0 .4μmol/L、0 .5μmol/L、0 .6μmol/L、0 .7μmol/L)作用下PS值在 70min内波动幅度随浓度升高而变小 ,70min末PS值百分比分别为1 93.8%、1 2 9%、75.2 % (恢复期末增大刺激强度 ,则可恢复到 1 0 0 % )、97.1 % .上述结果提示 :低浓度Glu( 1mmol/L ,1 .2 5mmol/L)对神经元具有兴奋作用 ;高浓度Glu( 2 .5mmol/L ,5mmol/L)具有神经毒性作用 ;MEL对神经元具有兴奋和抑制双重作用 ,因MEL浓度不同 ,其作用形式会有不同     

空间辨别性学习记忆活动对大鼠海马齿状回SDF-1免疫阳性细胞的影响

目的:探讨空间辨别性学习记忆活动引致大鼠海马形态学可塑与海马齿状回内基质细胞衍生因子-1(SDF-1)表达的关系。方法:用水迷宫训练SD大鼠建立空间辨别性学习记忆模型,用免疫组化方法和图像分析技术检测大鼠海马齿状回SDF-1免疫阳性细胞的变化。结果:(1)对照组大鼠海马齿状回可见少量SDF-1免疫阳性细胞,阳性细胞胞体呈圆形或椭圆形,胞核较大,胞浆呈棕黄色。阳性细胞主要分布在齿状回颗粒细胞层;游水组大鼠海马齿状回SDF-1免疫阳性细胞的数量和形态与对照组的相比未见差异;模型组大鼠海马齿状回SDF-1免疫阳性细胞数量随着训练时间逐渐增多,细胞形态同对照组,胞浆呈深棕黄色,并有一至多个突起。(2)对照组与游水组7、14、21 d的大鼠海马齿状回SDF-1免疫阳性细胞在形态和数量未见统计学差异(P>0.05);对照组与模型组7、14 d大鼠海马齿状回SDF-1免疫阳性细胞的形态和数量未见统计学差异(P>0.05);模型21 d大鼠齿状回SDF-1免疫阳性细胞的形态和数量与对照组的比有明显统计学差异(P<0.01)。结论:大鼠海马齿状回内SDF-1阳性细胞可能参与空间辨别性学习记忆活动引致的形态学可塑性。     

诺迪康对AD模型大鼠学习记忆及海马AchE、ChAT活性的影响

目的研究诺迪康对阿尔茨海默病(AD)模型大鼠学习记忆及海马胆碱能系统的影响.方法将32只SD大鼠随机分成4组:模型组,安理中组,诺迪康组和正常组.采用双侧海马内注射Aβ-40制作大鼠AD模型,采用Morris水迷宫检测诺迪康对AD大鼠认知功能的影响;通过HE染色观察对AD大鼠的海马神经元形态的影响;采用免疫组化法观察对...     

Adult hippocampal neurogenesis: regulation by HIV and drugs of abuse

New dentate granule cells are continuously generated from neural progenitor cells and integrated into the existing hippocampal circuitry in the adult mammalian brain through an orchestrated process termed adult neurogenesis. While the exact function remains elusive, adult neurogenesis has been suggested to play important roles in specific cognitive functions. Adult hippocampal neurogenesis is regulated by a variety of physiological and pathological stimulations. Here we review emerging evidence showing that HIV infection and several drugs of abuse result in molecular changes that may affect different aspects of adult hippocampal neurogenesis. These new findings raise the possibility that cognitive dysfunction in the setting of HIV infection or drug abuse may, in part, be related to alterations in hippocampal neurogenesis. A better understanding of how HIV and drugs of abuse affect both molecular and cellular aspects of adult neurogenesis may lead to development of more effective therapeutic interventions for these interlinked epidemics. Received 6 February 2007; received after revision 26 March 2007; accepted 25 April 2007