Receptor Trafficking and the Regulation of Synaptic Plasticity by SUMO

Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.     

覆膜支架在颈内动脉海绵窦段病变治疗中的应用

目的 评价应用覆膜支架治疗颈内动脉海绵窦段病变的价值.方法 采用覆膜支架治疗11例颈内动脉海绵窦段病变,其中颈内动脉海绵窦瘘5例,颈内动脉海绵窦段动脉瘤6例,术后1年行全脑血管造影随访和临床随访.结果 11例患者中,成功应用覆膜支架治疗9例,成功置入覆膜支架的9例患者,术后即刻血管造影显示病变完全消失,临床症状逐渐好转,无手术相关并发症,术后1年行全脑血管造影复查8例,结果显示病变消失,责任动脉均保持通畅.结论 覆膜支架在处理颈内动脉海绵窦段动脉瘤或颈内动脉海绵窦瘘方面,有治疗成功率高,疗效好,并发症少,复发率低等特点,值得推广.     

非痴呆性血管性认知功能障碍患者的脑电超慢涨落图表现

目的探讨主诉记忆力减退的非痴呆性血管性认知功能障碍(VCIND)患者脑内神经递质活动的变化及意义。方法选择2008—2012年第二炮兵总医院神经内科门诊患者716例,其中主诉记忆力减退的VCIND组370例,正常对照组346例。采用简易精神状态量表(MMSE)、蒙特利尔认知测评量表(MoCA)进行认知评估。应用脑电超慢涨落(EFG)分析仪测定S1γ-氨基丁酸(GABA)、S2谷氨酸(Glu)、S4 5-羟色胺(5-HT)、S5乙酰胆碱(Ach)、S7去甲肾上腺素(NE)、S11多巴胺(DA)等脑神经递质的活动。结果观察组GLU、5-HT的活动存在异常,GLU显著高于对照组(P<0.05),5-HT显著低于对照组(P<0.05);GABA、Ach、NE、DA的活动与对照组比较,差异无统计学意义(P>0.05)。结论主诉记忆力减退的VCIND人群脑内神经递质谷氨酸、5-羟色胺活动异常。EFG分析可作为一种有效的VCIND辅助诊断方法。     

An effective initial polytherapy for children with West syndrome

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B 6 , and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B 6 , and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin B 6 , and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.     

Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats

Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury (SCI), and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by multiple factors. Autophagy can result in cell death, and plays a key role in the development of SCI. It has been recognized that valproic acid (VPA) is neuroprotective in certain experimental animal models, however, the levels of autophagic changes in the process of neuroprotection by VPA treatment following SCI are still unknown. In the present study, we determined the extent of autophagy after VPA treatment in a rat model of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however, Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie-Bresnahan scale, increased the number of ventral horn motoneurons, and reduced myelin sheath damage compared with vehicle-treated animals at 42 days after SCI. Together, our results demonstrated the characteristics of autophagy expression following SCI, and found that VPA reduced autophagy and enhanced motor function.     

Use of antidepressants in the treatment of depression in Asia: Guidelines,clinical evidence,and experience revisited

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence‐based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence‐based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.     

State-Dependent Effects of Prefrontal Repetitive Transcranial Magnetic Stimulation on Emotional Working Memory

BackgroundA growing body of findings illustrates the importance of state-dependency in studies using brain stimulation.ObjectiveWe aimed to investigate the effects of tDCS priming followed by rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) on emotional working memory.MethodsIn a randomized single-blind within-subjects design, participants performed an emotional 3-back task at baseline and after tDCS priming (anodal, cathodal) and subsequent low-frequency rTMS (active, sham) of the right DLPFC. Stimuli consisted of words related to the distinct emotion categories fear and anger as well as neutral words.ResultsTask accuracy increased for fear-related words and decreased for neutral words across stimulation conditions. No general state-dependent effects of prefrontal rTMS on working memory were found. We further showed a detrimental effect of negative emotional content on working memory performance.ConclusionsOur findings support a hemispheric lateralization of emotion processing by demonstrating that the withdrawal-related emotion fear is associated with the right DLPFC and contribute to clarifying the interaction between working memory and emotion.