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。     

Inhibition of mGluR1 and IP3Rs impairs long-term memory formation in young chicks

Calcium (Ca²⁺) is involved in a myriad of cellular functions in the brain including synaptic plasticity. However, the role of intracellular Ca²⁺ stores in memory processing remains poorly defined. The current study explored a role for glutamate-dependent intracellular Ca²⁺ release in memory processing via blockade of metabotropic glutamate receptor subtype 1 (mGluR1) and inositol (1,4,5)-trisphosphate receptors (IP₃Rs). Using a single-trial discrimination avoidance task developed for the young chick, administration of the specific and potent mGluR1 antagonist JNJ16259685 (500 nM, immediately post-training, ic), or the IP₃R antagonist Xestospongin C (5 μM, immediately post-training, ic), impaired retention from 90 min post-training. These findings are consistent with mGluR1 activating IP₃Rs to release intracellular Ca²⁺ required for long-term memory formation and have been interpreted within an LTP2 model. The consequences of different patterns of retention loss following ryanodine receptor (RyR) and IP₃R inhibition are discussed.     

Co-induction of long-term potentiation and long-term depression at a central synapse in the leech

Most studies of long-term potentiation (LTP) have focused on potentiation induced by the activation of postsynaptic NMDA receptors (NMDARs). However, it is now apparent that NMDAR-dependent signaling processes are not the only form of LTP operating in the brain [Malenka, R. C., & Bear, M. F. (2004). LTP and LTD: An embarrassment of riches. Neuron, 44, 5–21]. Previously, we have observed that LTP in leech central synapses made by the touch mechanosensory neurons onto the S interneuron was NMDAR-independent [Burrell, B. D., & Sahley, C. L. (2004). Multiple forms of long-term potentiation and long-term depression converge on a single interneuron in the leech CNS. Journal of Neuroscience, 24, 4011–4019]. Here we examine the cellular mechanisms mediating T-to-S (T → S) LTP and find that its induction requires activation of metabotropic glutamate receptors (mGluRs), voltage-dependent Ca²⁺ channels (VDCCs) and protein kinase C (PKC). Surprisingly, whenever LTP was pharmacologically inhibited, long-term depression (LTD) was observed at the tetanized synapse, indicating that LTP and LTD were activated at the same time in the same synaptic pathway. This co-induction of LTP and LTD likely plays an important role in activity-dependent regulation of synaptic transmission.     

Habituation in Aplysia: The Cheshire Cat of neurobiology

The marine snail, Aplysia californica, is a valuable model system for cell biological studies of learning and memory. Aplysia exhibits a reflexive withdrawal of its gill and siphon in response to weak or moderate tactile stimulation of its skin. Repeated tactile stimulation causes this defensive withdrawal reflex to habituate. Both short-term habituation, lasting <30 min, and long-term habituation, which can last >24 h, have been reported in Aplysia. Habituation of the withdrawal reflex correlates with, and is in part due to, depression of transmission at the monosynaptic connection between mechanoreceptive sensory neurons and motor neurons within the abdominal ganglion. Habituation-related short-term depression of the sensorimotor synapse appears to be due exclusively to presynaptic changes. However, changes within the sensory neuron, by themselves, do not account for more persistent depression of the sensorimotor synapse. Recent behavioral work suggests that long-term habituation in Aplysia critically involves postsynaptic processes, specifically, activation of AMPA- and NMDA-type receptors. In addition, long-term habituation requires activity of protein phosphatases, including protein phosphatases 1, 2A, and 2B, as well as activity of voltage-dependent Ca²⁺ channels. Cellular work has succeeded in demonstrating long-term, homosynaptic depression (LTD) of the sensorimotor synapse in dissociated cell culture and, more recently, LTD of the glutamate response of isolated motor neurons in culture (“hemisynaptic” LTD). These in vitro forms of LTD have mechanistic parallels to long-term habituation. In particular, homosynaptic LTD of the sensorimotor synapse requires elevated intracellular Ca²⁺ within the motor neuron, and hemisynaptic LTD requires activity of AMPA- and NMDA-type receptors. In addition, activation of group I and II metabotropic glutamate receptors (mGluRs) can induce hemisynaptic LTD. The demonstration of LTD in vitro opens up a promising new avenue for attempts to relate long-term habituation to cellular changes within the nervous system of Aplysia.     

Fatty acid amide hydrolase (FAAH) knockout mice exhibit enhanced acquisition of an aversive, but not of an appetitive, Barnes maze task

It is well established that genetic deletion or pharmacological inhibition of the CB₁ receptor disrupts extinction learning in aversive conditioning tasks, but not in appetitive tasks. Consistent with these findings is that genetic deletion or pharmacological inhibition of fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of the endogenous cannabinoid anandamide (AEA), accelerates acquisition as well as extinction in aversive conditioning tasks. However, it is unknown whether FAAH blockade will affect acquisition in an appetitive conditioning task. Therefore, in the present study, we assessed FAAH (−/−) and (+/+) mice in appetitive and aversive Barnes maze conditioning procedures. Here we report that FAAH (−/−) mice displayed accelerated acquisition rates in an aversively-motivated, but not in the appetitively-motivated, Barnes maze task. The CB₁ receptor antagonist, rimonabant attenuated enhanced acquisition in the aversive procedure, consistent with the idea that elevated AEA levels mediate this apparent nootropic effect. These findings support the hypothesis that stimulation of the endocannabinoid system enhances learned behavior in aversive, but not appetitive, conditioning paradigms.