Pleasurable behaviors reduce stress via brain reward pathways

Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.     

复合微量营养素对幼鼠学习记忆能力及脑海马CA3超微结构的影响

目的研究复合微量营养素对幼年大鼠学习记忆能力的影响及其机制。方法5周龄雄性SD大鼠40只,按体重随机分成3个实验组和1个对照组。实验组分别以低、中、高剂量复合微量营养素水悬液灌胃,对照组用安慰剂水悬液灌胃。30天后各组大鼠每隔1天在穿梭箱中进行双向回避实验训练,连续训练4次后,停止训练,并在14天内分2次测定其记忆消退情况;用电镜观察海马CA3区突触结构的变化;用免疫组织化学方法检测大鼠海马突触素(Syn)的免疫表达。结果高剂量组大鼠电击逃避时间长于对照组(P<0.05);高剂量组大鼠脑海马CA3区突触数量、突触后致密物质厚度、突触界面曲率、Syn免疫反应阳性产物吸光度均显著高于对照组(P<0.05);电击逃避时间和突触界面曲率呈剂量效应关系。结论复合微量营养素能通过提高大鼠脑海马的突触可塑性来改善幼年大鼠学习记忆能力。     

The synapsins: Key actors of synapse function and plasticity

The synapsins are a family of neuronal phosphoproteins evolutionarily conserved in invertebrate and vertebrate organisms. Their best-characterised function is to modulate neurotransmitter release at the pre-synaptic terminal, by reversibly tethering synaptic vesicles (SVs) to the actin cytoskeleton. However, many recent data have suggested novel functions for synapsins in other aspects of the pre-synaptic physiology, such as SV docking, fusion and recycling. Synapsin activity is tightly regulated by several protein kinases and phosphatases, which modulate the association of synapsins to SVs as well as their interaction with actin filaments and other synaptic proteins. In this context, synapsins act as a link between extracellular stimuli and the intracellular signalling events activated upon neuronal stimulation. Genetic manipulation of synapsins in various in vivo models has revealed that, although not essential for the basic development and functioning of neuronal networks, these proteins are extremely important in the fine-tuning of neuronal plasticity, as shown by the epileptic phenotype and behavioural abnormalities characterising mouse lines lacking one or more synapsin isoforms.     

Biomechanical properties and innervation of the female caveolin-1-deficient detrusor

BACKGROUND AND PURPOSE

Caveolin-1-deficiency is associated with substantial urogenital alterations. Here, a mechanical, histological and biochemical characterization of female detrusors from wild-type and caveolin-1-deficient (KO) mice was made to increase the understanding of detrusor changes caused by lack of caveolae.

EXPERIMENTAL APPROACH

Length–tension relationships were generated, and we recorded responses to electrical field stimulation, the muscarinic receptor agonist carbachol and the purinoceptor agonist ATP. Tyrosine nitration and the contents of caveolin-1, cavin-1, muscarinic M₃ receptors, phospholipase C_β1, muscle-specific kinase (MuSK) and L-type Ca²⁺ channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry.

KEY RESULTS

Bladder to body weight ratio was not changed, nor was there any change in the optimum circumference for force development. Depolarization- and ATP-induced stress was reduced, as was carbachol-induced stress between 0.1 and 3 µM, but the supramaximal relative (% K⁺) response to carbachol was increased, as was M₃ expression. The scopolamine-sensitive component of the electrical field stimulation response was impaired, and yet bladder nerves contained little caveolin-1. The density of cholinergic nerves was unchanged, whereas CART- and CGRP-positive nerves were reduced. Immunoblotting revealed loss of MuSK.

CONCLUSIONS AND IMPLICATIONS

Ablation of caveolae in the female detrusor leads to generalized impairment of contractility, ruling out prostate hypertrophy as a contributing factor. Cholinergic neuroeffector transmission is impaired without conspicuous changes in the density of cholinergic nerves or morphology of their terminals, but correlating with reduced expression of MuSK.     

运动对快速老化小鼠海马突触素表达的影响

目的研究运动对快速老化小鼠（SAMP8）海马突触素表达的影响,探讨运动改善阿尔茨海默病（AD）学习记忆功能的机制。方法 3月龄SAMP8小鼠40只随机分为运动组（采用跑笼运动训练）和对照组,2个月后HE染色观察2组海马神经元形态改变;免疫组化技术检测2组海马突触素表达。结果 5月龄SAMP8小鼠对照组海马部分神经元细胞变性、死亡,核浓缩,空泡变性;运动组偶有神经元细胞变性、死亡,大部分细胞形态正常。海马突触素表达运动组较对照组显著增高（P〈0.05）。结论运动可以延缓SAMP8小鼠海马神经元变性,提高海马突触素表达,这可能是运动改善AD学习记忆功能的重要机制之一。     

体外培养大鼠脊髓前角神经元：脑源性神经生长因子对突触蛋白表达的影响

探讨BDNF对体外培养的大鼠脊髓前角神经元内突触素I与突触囊泡素(SYN)表达的影响。取孕14 d大鼠子宫内胎鼠的脊髓腹侧部分神经元,体外有血清培养。在培养7 d后．随机分成对照组、BDNF组和抗BDNF组。BDNF组培养液中加入BDNF(20 ng/ml),抗BDNF组培养液中加入BDNF抗体(20цg/ml),对照组加入等量Hanks液。3 d后在倒置显微镜下计数三组神经元成活数,并用NF-200、MAP-2、NSE的免疫组化反应对神经细胞进行鉴定。行突触素I与SYN免疫组化反应,对部分细胞行突触素I mRNA原位杂交反应,运用图像分析系统对突触素I与SYN免疫反应阳性产物以及突触素I原位杂交反应阳性产物作光密度分析。结果发现有血清培养时各组脊髓前角神经元的存活数差异无显著性 (P>0.05);BDNF组突触素I与SYN免疫反应阳性产物的平均光密度值高于其它两组,抗BDNF组最低（P<0.01）。BDNP组突触素I mRNA阳性产物的平均光密度值明显高于其它两组,抗BDNF组突触素I mRNA阳性产物的平均光密度值最低（P<0.01）。本研究结果提示BDNF对有血清培养时脊髓前角神经元的存活没有明显影响,但BDNF可明显上调培养的脊髓前角神经元内突触素I与SYN的表达     

丰富环境干预对慢性低灌注血管性痴呆大鼠学习记忆及突触素蛋白和微管相关蛋白的影响

目的:观察丰富环境干预对慢性低灌注血管性痴呆大鼠学习记忆能力、海马突触素(SYN)蛋白及微管相关蛋白-2(MAP-2)表达的影响。方法:雄性SD大鼠随机分为正常对照组、模型组、丰富环境组。双侧颈总动脉永久性结扎制备慢性低灌注大鼠模型。丰富环境干预50d后,利用Morris水迷宫检测学习记忆功能;免疫组织化学法检测SYN、MAP-2的表达。结果:慢性低灌注大鼠空间参考记忆能力下降,搜索隐藏平台的逃避潜伏期和游泳路径明显延长;定位记忆障碍,在空间探索实验中准确穿越平台位置的次数减少;工作记忆明显损害,寻找移动平台的逃避潜伏期及游泳路径比正常大鼠明显延长(P0.01或P0.05)。海马CA1、CA3区SYN、MAP-2的免疫反应明显减弱(P0.01)。丰富环境干预后,大鼠搜索隐匿平台的逃避潜伏期和游泳路径均有不同程度的缩短,准确穿越平台所在位置的次数比模型组增加;移动平台位置后,动物找到平台的时间和游泳路径明显比模型组缩短(P0.01或P0.05);海马区SYN、MAP-2的积分光密度值均有不同程度增加(P0.01或P0.05)。结论:丰富环境干预可改善慢性低灌注大鼠学习记忆能力,其作用与上调海马SYN、MAP-2蛋白表达,提高突触可塑性有关。     

知母总皂苷对老年大鼠学习记忆行为和海马突触相关蛋白表达的影响

目的探讨知母总皂苷(SAaB)对老年大鼠学习记忆能力及突触相关蛋白表达的影响。方法 ig给予18个月龄SD大鼠SAaB 100和200 mg.kg-1,每天1次,连续9周,第8周开始进行Morris水迷宫实验,记录逃避潜伏期及各象限游泳时间。免疫组织化学法观察海马突触素蛋白(SYP)分布。Western印迹法检测CA3区SYP、突触后致密蛋白95(PSD95)、磷酸化蛋白激酶B(p-Akt)和磷酸化雷帕霉素靶蛋白(p-mTOR)蛋白分布。结果与青年大鼠对照组比较,老年对照组大鼠逃避潜伏期显著增加,原平台象限游泳时间占总时间的百分比显著缩短(P<0.05),海马SYP,PSD95,p-Akt和p-mTOR表达显著降低(P<0.01)。与老年对照组相比,给予SAaB后,青年大鼠逃避潜伏期显著缩短,原平台象限游泳时间占总时间的百分比显著增加(P<0.05);海马SYP,PSD95,p-Akt和p-mTOR表达显著增加(P<0.01)。结论 SAaB能显著改善老年大鼠学习记忆能力,可能与上调SYP和PSD95表达及激活Akt/mTOR信号通路有关。     

经颅重频磁刺激增强大鼠大脑中动脉梗塞再灌注损伤后神经重塑

目的 通过观察大鼠大脑中动脉缺血再灌注损伤后7 d,大鼠神经功能、生长相关蛋白-43(GAP-43)、突触素(SYN)表达的变化,探讨经颅重频磁刺激(rTMS)对缺血性损伤后脑组织可塑性的影响.方法 制作大鼠右侧大脑中动脉梗塞再灌注模型,连续7 d给予不同频率和强度的rTMS,同时设立假刺激组和假手术组进行对照.观察大...     

Distinct α GABA(A)R subunits influence structural and transcriptional properties of CA1 hippocampal neurons

The hippocampus is recognized as a major telencephalic area modulating learning and episodic memory through the activation of its different subregions. The various functional properties of Ammon's horn 1 (Cornu Amonis 1; CA1) area have been shown to rely on GABAergic and Glutamat- (Glu)-ergic neuronal signals during both postnatal and adult stages. For this purpose, it was the aim of the present study to establish whether certain alpha GABA(A)R subunits (alpha(2,5)) were capable of modifying CA1 structural and functional features via their interaction with specific NMDA receptor subunits such as NR1 during early development stages of the hibernating hamster (Mesocricetus auratus). Indeed, in vitro addition of the selective alpha(2,5) GABA(A)R agonist diazepam (DZP; alpha(2,5)) accounted for early neuronal formations that were blocked by its antagonist flumazenil (FLM). In particular, the former drug caused very great (p<0.001) increases of dendritic sprouting and branching processes mainly at day in vitro (DIV) 3, while its effects still continued to be responsible for moderate (p<0.05) increases of axonal length during the entire culture period. Contextually, DZP was also responsible for a very great up-regulated expression of neuritic NR1 and MAP2 together with a great (p<0.01) increase of synaptophysin at DIV7. Overall, this first study suggests a specifically tight cross-talking relationship of GABAergic/Gluergic mechanisms operating during CA1 neuronal development, which may bring us closer to the identification of more selective therapeutic targets for hippocampal-linked neurological disorders.