Memory related molecular signatures: The pivots for memory consolidation and Alzheimer's related memory decline

Age-related cognitive decline is the major cause of concern due to its 70% more incidence than dementia cases worldwide. Moreover, aging is also the major risk factor of Alzheimer's disease (AD), associated with progressive memory loss. Approx. 13 million people will have Alzheimer-related memory decline by 2050. Learning and memory is the fundamental process of brain functions. However, the mechanism for the same is still under investigation. Thus, it is critical to understand the process of memory consolidation in the brain and extrapolate its understanding to the memory decline mechanism. Research on learning and memory has identified several molecular signatures such as Protein kinase M zeta (PKMζ), Calcium/calmodulin-dependent protein kinase II (CaMKII), Brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) and Activity-regulated cytoskeleton-associated protein (Arc) crucial for the maintenance and stabilization of long-term memory in the brain. Interestingly, memory decline in AD has also been linked to the abnormality in expressing these memory-related molecular signatures. Hence, in the present consolidated review, we explored the role of these memory-related molecular signatures in long-term memory consolidation. Additionally, the effect of amyloid-beta toxicity on these molecular signatures is discussed in detail.     

Implementation of Nurse-Led Cognitive Screening During Medicare Annual Wellness Visits

Dementia is a serious and costly illness. Early identification of cognitive impairment provides opportunity for earlier intervention, and there is growing evidence suggesting that early intervention may help delay the onset of dementia. There is limited concensus and standardized recommendations for when and how cognitive screening should occur. This quality improvement project implemented a standardized nurse-led cognitive screening workflow during the Medicare annual wellness visit. Statistically significant differences were found between the baseline and implementation groups for Mini-Cog screening rates and referral for follow-up for further neurocognitive evaluation. A structured nurse-led workflow improved the cognitive screening process, providing opportunity for further evaluation and intervention.     

腰椎棘突间记忆合金动态稳定装置理论验证

为了在腰椎退变性疾病保守治疗和融合手术中间地带寻找一种有效的预防与辅助相结合的微创治疗方式,通过对比目前常用的几种腰椎棘突间动态稳定系统的临床疗效观察和优缺点,以及对腰椎棘突间的生理结构、生物力学和相关数据的分析,在充分了解记忆合金材质的基础上,自行设计研究一种记忆合金材料的新型腰椎棘突间动态固定装置,既能重建腰椎的正常生物力学特性,满足人体脊柱的正常活动,又避免对原有结构的破坏,减少术后并发症的发生,同时也可以优化目前的治疗方法。通过研究,腰椎棘突间记忆合金动态稳定装置在理论上效果满意,可以解决现有技术的不足,优于目前的几种腰椎棘突间动态稳定系统。     

Residential greenness and risks of depression: Longitudinal associations with different greenness indicators and spatial scales in a Finnish population cohort

We carried out a longitudinal study on the associations between residential greenness and depression risk in urban areas in Finland. Residential greenness indicators were estimated within various buffer sizes around individuals' home locations (selected n = 14424) using time-series of normalized differential vegetation index (NDVI) and CORINE land cover data (CLC). We estimated individuals’ cumulative exposure to residential greenness over a 5-years and 14-years follow-up. We used doctor-diagnosed depression and Beck Depression Inventory for depression assessment. Our multi-logistic model showed an inverse association between residential greenness and depression, implying lowered depression risk for individuals with higher residential greenness. The association was particularly evident when using NDVI-based residential greenness (within a buffer of 100 m radius) and doctor-diagnosis depression data, adjusted with individual-level covariates. The odds ratio was 0.56 (95% CI 0.33 to 0.96) for the 5-years follow-up, and 0.54 (95% CI 0.30 to 0.98) for the 14-years follow-up. The associations between CLC-based total residential green space and depression varied across the different buffer sizes. In general, all the associations depended on the type of depression assessment, quality of greenness indicators, and the spatial scale of analysis. The associations also varied across the socio-demographic groups and neighborhood socioeconomic disadvantage level.     

六味地黄汤干预抑郁大鼠学习记忆的作用机制

目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。     

鲜天麻对睡眠干扰诱导小鼠学习记忆障碍的改善作用

目的研究鲜天麻对睡眠干扰(sleep interruption,SI)诱导的小鼠学习记忆障碍的改善作用。方法 HPLC法测定鲜天麻中天麻素、对羟基苯甲醇的含量,苯酚硫酸法测定多糖的含量。60只ICR雄鼠随机分为对照组、睡眠干扰模型组、阳性药(莫达非尼)组和鲜天麻低(3 g/kg)、高(9 g/kg)剂量组。睡眠干扰造模14 d后,依次进行自主活动、新物体识别、水迷宫和避暗等动物行为学检测实验,并测定小鼠血清和海马组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平及海马组织乙酰胆碱(Ach)、谷氨酸(Glu)和去甲肾上腺素(NE)水平。结果自主活动实验中,各组小鼠运动功能无显著性差异。与对照组比较,模型组小鼠在新物体识别实验中的相对辨别指数(DI)显著性下降,水迷宫寻台潜伏期明显延长,避暗实验错误次数增加、入暗潜伏期缩短;血清和海马组织MDA水平升高,海马组织的SOD水平降低;海马组织Ach、Glu和NE水平均显著降低。与模型组比较,莫达非尼和鲜天麻各剂量能不同程度增加小鼠新物体识别DI,提高新物体辨别能力;增强空间学习获得和保持能力,缩短水迷宫潜伏期;减少避暗错误次数、延长避暗潜伏期;提高血清和海马组织中SOD、Ach、Glu和NE水平,降低MDA水平。结论鲜天麻能改善睡眠干扰引起的学习记忆障碍,改善氧化应激和神经递质水平,是一种有潜力的改善学习记忆中药。     

空间统计学在食品污染物分布研究中的应用

目的 以2017年某省食品安全监测大米中砷含量数据为例，探讨空间统计学方法在食品污染物分析中的应用价值。方法 采用空间点模式估计、核密度分析，全局以及局部自相关性分析等空间统计学方法，在县级空间尺度下，对某省大米中砷含量进行探索性空间数据分析。结果 空间点模式分布图显示，该省大米砷污染的空间分布比较分散，核密度分析结果显示污染热点区域主要在该省中东部地区。全局自相关Moran''s I指数值为0.11，有统计学意义，大米样品中砷污染呈现出低度空间聚集性。有1个"高-高"聚集区，2个典型的"低-低"聚集区。结论 空间统计学运用于食物污染物分布研究上，可以很好地可视化展示、识别污染分布规律、热点地区和聚集区，为基于问题的监测工作的开展提供技术支持。     

大补元煎通过上调BDNF/TrkB/CREB信号通路改善APP/PS1双转基因痴呆小鼠海马突触可塑性

目的:观察大补元煎对APP/PS1痴呆小鼠海马突触可塑性及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的作用,并探讨其改善突触可塑性的可能机制。方法:将APP/PS1小鼠36只分为模型组、多奈哌齐组(6.5×10~(-4)g·kg~(-1)·d~(-1))和大补元煎组(13.2 g·kg~(-1)·d~(-1)),野生鼠12只设为正常组,正常组和模型组给予等体积生理盐水,各组连续灌胃30 d。应用Morris水迷宫检测各组小鼠的学习记忆能力,应用尼氏染色和高尔基染色观察海马区神经元和突触的病理形态变化,应用免疫荧光(IF)观察海马突触后致密蛋白95(PSD95)及突触素(SYN)的蛋白表达水平,采用蛋白免疫印迹法(Western blot)检测海马中BDNF,TrkB,CREB及磷酸化CREB(p-CREB)的蛋白表达水平。结果:与空白组比较,模型组小鼠平台潜伏期和游泳总路程增加(P0.01),穿越平台次数和目标象限停留时间减少(P0.01),小鼠海马CA3区神经元胞内尼氏体减少或消失,小鼠海马CA3区神经元及树突分支数量、树突棘密度减少(P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平减少(P0.01)。与模型组比较,多奈哌齐组和大补元煎组小鼠平台潜伏期和游泳总路程减少(P0.05,P0.01),穿越平台次数和目标象限停留时间增加(P0.05,P0.01),小鼠海马CA3区神经元胞内尼氏体数量增多,小鼠海马CA3区神经元及树突分支数量,树突棘密度增加(P0.05,P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平增加(P0.05,P0.01)。结论:大补元煎改善APP/PS1双转基因小鼠突触可塑性的机制可能与其上调小鼠海马中BDNF/TrkB/CREB信号通路有关。     

Modulating reconsolidation and extinction to regulate drug reward memory

Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug‐associated cues could result in reconsolidation, a hypothetical process during which original memory could be updated. In contrast, longer exposure times to drug‐associated cues could trigger extinction, a process that decreases the conditioned responding. In this review, we discuss the pharmacological and non‐pharmacological manipulations on the reconsolidation and extinction that could be used to interfere with drug reward memories. Pharmacological agents such as β‐adrenergic receptor antagonist propranolol can interfere with reconsolidation to disrupt drug reward memory. Pharmacological agents such as the NMDA receptor glycine site agonists d ‐cycloserine and d ‐serine can facilitate extinction and then attenuate the expression of drug reward memory. Besides pharmacological interventions, drug‐free behavioral approaches by utilizing the reconsolidation and extinction, such as ‘post‐retrieval extinction’ and ‘UCS‐retrieval extinction’, are also effective to erase or inhibit the recall of drug reward memory. Taken together, pharmacological modulation and non‐pharmacological modulation of reconsolidation and extinction are promising approaches to regulate drug reward memory and prevent relapse.