Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat

Adenosine A1 and A2A receptor agonists and antagonists have been reported to alter learning and memory. The aim of our study was to investigate the involvement of adenosinergic system in memory retrieval into posterior cingulate cortex (PCC) of Wistar rats. To clarify this question, we tested specifics agonist and antagonists of adenosine A1 and A2A receptors in rats submitted to a one-trial inhibitory avoidance task. The stimulation of adenosine A1 and A2A receptors by CPA and CGS21680, respectively, impaired memory retrieval for inhibitory avoidance task, into PCC. These findings provide behavioral evidence for the role of adenosinergic system in the memory retrieval into PCC.     

Non-ligand activation of estrous behavior in rodents: cross-talk at the progesterone receptor

Estrous behavior in rodents is triggered by the binding of progesterone (P) to its intracellular receptor (PR). Non-steroidal agents (i.e., gonadotropin-releasing hormone, noradrenaline, dopamine and others), acting at the membrane, can facilitate estrous behavior in estrogen-primed rats. This action is mediated through the generation of second messengers (cyclic AMP, cyclic GMP, calcium) which, in turn, phosphorylate through diverse kinase systems (protein kinases A, G or C) either the PR or associated effector proteins linking the PR to the trans-activation machinery. P or its metabolites also activate cyclic AMP-signaling pathways by acting directly on the membrane or by modulating neurotransmitter release. Molecular processes resulting from second messenger signaling pathways and those from the progesterone-RP interaction synergize to elicit a full behavioral response.     

Septal infusions of glucose or pyruvate,but not fructose,produce avoidance deficits when co-infused with the GABA agonist muscimol

Although glucose typically enhances memory or reverses memory deficits, glucose can also produce memory deficits when co-infused with the gamma-aminobutyric acid (GABA) agonist muscimol into the medial septum (Parent & Gold, 1997; Parent, Laurey, Wilkniss, & Gold, 1997). To date the mechanisms underlying the memory-impairing interaction between GABA and glucose remain unknown. Here we investigate whether this effect is the result of hyperosmolar conditions or may involve glucose metabolism. Male Sprague-Dawley rats were given one-trial inhibitory avoidance training after receiving septal infusions of vehicle (phosphate-buffered saline, 0.5 microl), the GABA(A) agonist muscimol (3 nmol), glucose (16.5, 33, or 66 nmol), fructose (33 nmol), pyruvate (33 nmol), or a solution containing muscimol combined with glucose, fructose, or pyruvate. Retention performance was tested 48 h later. Infusions of glucose, pyruvate, fructose, or muscimol alone did not affect retention performance. However, co-infusions of all doses of glucose (16.5, 33, or 66 nmol) or the glycolytic end product pyruvate with muscimol impaired retention performance. Co-infusions of fructose with muscimol did not affect retention performance. These results suggest that the memory-impairing interaction between glucose and muscimol does not result from hyperosmolar conditions, because equiosmolar concentrations of fructose do not mimic the effects of glucose and the memory deficits do not vary as a function of glucose concentration. The finding that pyruvate mimicked the effects of glucose and impaired memory when combined with muscimol suggests that glucose metabolism may be involved in the memory-impairing interaction between glucose and GABA(A) receptors in the medial septum.     

人是怎样与世界统一的——一个关于细胞信息跨膜传递特异性的假说

本文在讨论有限和无限的对立统一规律在抗原和抗体产生机制中的体现的基础上,提出关于细胞信息跨膜传递特异性机制的假说：第一信使可能由有限的基本单位构成,其信息的特异性可能通过有限的信息中介的组合来得以体现,效应部位也可能因具有特定的信息中介结合位点的组合而产生特异的细胞效应。本文最后为这一假说的证实提出展望。     

Differential Effect of TEA on Long-Term Synaptic Modification in Hippocampal CA1 and Dentate Gyrus in vitro

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni²⁺ (50 μM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni²⁺ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 μM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni²⁺. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni²⁺. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.     

公众对活体大器官移植的认知态度与对策

对河南地区公众关于活体大器官移植态度进行的抽样调查结果显示：（1）公众赞成开展活体大器官移植;（2）多数公众反对器官买卖,但赞成器官买卖的也有相当大的比例;（3）亲情是亲属活体器官捐献者愿意捐献的主要原因。针对调查结果,我们在比较分析的基础上,提出了相关对策,促使活体大器官移植技术更好地造福于人类。     

中枢N-甲基-D-天冬氨酸受体在应激所致行为改变中的作用

应激所致行为效应的脑机制研究是目前生理心理学研究的热点领域。近年来,对于参与应激所致行为效应的神经递质研究从5-HT、多巴胺和去甲肾上腺素的范畴,逐渐发展到关注脑内含量最为丰富的谷氨酸能神经元所产生的兴奋性递质,包括谷氨酸、天冬氨酸及其相应受体NMDAR可能在应激性行为效应的中枢机制中的作用。近十年来的研究表明,中枢NMDAR是学习记忆的关键物质,在兴奋性突触传递、突触可塑性和脑发育过程中扮演重要的角色。不同类型的应激能导致动物的与行为密切相关脑区如杏仁核,海马的兴奋性氨基酸及NMDAR数量增多,活性增高。突触间隙增多的兴奋性氨基酸与NMDAR结合后,通过激活NMDAR促进糖皮质激素的相关性释放,共同产生的兴奋毒性作用引起上述脑区的神经元细胞缺失和变性;或干扰其他中枢神经递质在动物行为的脑内奖赏机制中的正常功能;或通过持续激活NMDAR,导致细胞内Ca2＋超载,损害其信号传导途径下游的蛋白激酶级联反应,使其底物蛋白的磷酸化或去磷酸化作用发生改变,影响突触可塑性和神经细胞间的信号传递,导致动物出现相应的行为障碍。应激前给动物的上述脑区注射NMDAR阻滞剂,可以减轻动物的应激性焦虑和抑郁行为。而NMDAR依赖性LTP下游途径的新信号分子,神经颗粒素,参与了脑内多种蛋白信号传导,可能是应激性行为效应的另一重要中枢机制。     

慢性应激性抑郁发生中大鼠眶额叶多巴胺D1受体对谷氨酸及其NMDA受体的调节

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid, Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体的NR2B亚基的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS)抑郁模型, 结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390, 运用糖水偏爱测试、悬尾实验和敞箱实验等方法检测动物的行为表现, 采用高效液相色谱法(high-performance liquid chromatography, HPLC)和蛋白质免疫印迹法(Western blot, WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。结果显示, 与对照组相比, CUMS组大鼠表现出明显的抑郁样行为变化, 且眶额叶多巴胺含量降低, 其D1型受体表达降低, 谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调; 注射SKF38393后可明显改善应激引起的抑郁样行为, 且眶额叶谷氨酸含量显著下降, NMDA受体的NR2B亚基表达也有所降低; 正常大鼠注射多巴胺D1受体拮抗剂SCH23390, 大鼠表现出和CUMS模型组相似的抑郁样行为, 且眶额叶谷氨酸含量升高, 其NMDA受体的NR2B亚基也明显上调。以上结果表明, 慢性不可预见性应激可能使眶额叶多巴胺释放减少, 从而使谷氨酸过量释放, NMDA受体过度激活, 导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。     

NR3C1基因多态性及单倍型、父母教养方式对青少年焦虑障碍的影响

NR3C1参与HPA轴调节,与应激相关的身心疾病关系密切。以往针对NR3C1与焦虑障碍的研究基本以成人为考察对象,且大多关注负性生活事件等个体层面环境变量。本研究采用病例-对照设计,以238名青少年为被试(焦虑障碍117人,对照121人),旨在考察NR3C1常见位点rs6191、rs6196、rs41423247的多态性、单倍型以及父母不同类型教养方式对焦虑障碍的影响。结果表明rs6191 GG基因型、rs6196 AA基因型、rs41423247 GG基因型与低焦虑障碍风险相关。父母过多的过度保护与冷漠拒绝、父亲过少的温暖关怀可预测较高的焦虑障碍风险。rs41423247多态性与母亲温暖关怀存在交互作用:rs41423247 GG基因型只在母亲温暖关怀较多时能降低焦虑障碍风险,在母亲温暖关怀较少时与焦虑障碍并无显著相关。此外,rs6191-rs6196-rs41423247构成的单倍型GAG与低焦虑障碍风险显著关联,TGC与高焦虑障碍风险显著关联,且二者与母亲温暖关怀、母亲过度保护分别存在交互作用。未来可采用追踪研究,从表观遗传层面探讨教养方式与NR3C1影响焦虑障碍的内在机制。     

关于B族Ⅰ型清道夫受体研究进展的认识

B族I型清道夫受体(SR-BI)具有经典的清道夫受体功能,且是HDL的高亲和力受体,并能介导HDL中胆固醇的选择性摄取、影响血浆HDL-C水平以及介导非酯化胆固醇在脂蛋白和细胞之间的双向运动,具有抗动脉粥样硬化的作用。其研究过程反映了相对真理与绝对真理、现象与本质的辩证关系。当新现象被逐一发现,相对真理就逐渐确立,而循序渐进并运用创造性思维,最终将揭示事物的本质,实现相对真理向绝对真理的转化。