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.     

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。     

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。     

Serum TLR2 and TLR4 levels in colorectal cancer and their association with systemic inflammatory markers,tumor characteristics,and disease outcome

Toll‐like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II–IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5‐year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.     

Functional MRI activation patterns of cerebellum in patients with epilepsy and brain tumors

Function of cerebellum in control and coordination of motor function has been well established for several years. Recent functional magnetic resonance imaging (MRI) studies reveal activation of cerebellum with memory, speech and language tasks. We hypothesize that during every function in the brain signals are relayed to cerebellum. We seek to analyze cognitive, emotional and social functions of cerebellum in patients with brain tumors and epilepsy utilizing functional Magnetic Resonance Imaging. Fifty‐one consecutive adult patients who underwent functional MRI examination were retrospectively analyzed for various activation patterns involving cerebellum. The neuropsychological battery of tasks assessed motor, language, memory, visual and auditory functions. Cognitive ability of all participants was assessed by Montreal cognitive assessment (MOCA). Patterns were analyzed for specific lobes and locations in the cerebellum. We found that simultaneous cerebellar activation is a consistent finding with brain activation during every functional MRI task that we tested except visual task. The patterns of functional MRI cerebellar activation were similar in both patient subgroups and control subjects compared to previously described patterns in normal subjects. Clin. Anat. 32:1053–1060, 2019. © 2019 Wiley Periodicals, Inc.     

Female rats are more vulnerable to lasting cognitive impairment after isoflurane exposure on postnatal day 4 than 7

Background

The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested.