西红花苷对阿尔茨海默病大鼠学习记忆及海马LTP的影响

目的:探讨西红花苷对阿尔茨海默病(Alzheimer’s disease,AD)大鼠空间学习记忆能力对海马LTP的影响。方法:健康成年SD大鼠,随机分为正常对照组、AD模型组、西红花苷(低、中、高剂量)组Morris水迷宫实验检测空间学习记忆能力,电生理实验检测海马LTP,Western Blot检测海马GAP-43蛋白表达。结果:AD模型组大鼠寻找水下平台的潜伏期时间较对照组延长(P0.01),西红花苷各剂量组寻找水下平台的潜伏期时间从第二天起,较AD模型组均缩短(P0.01),西红花苷中剂量组和高剂量组的潜伏期时间均短于低剂量组(P0.05),中、高剂量组间的潜伏期时间在各实验日均未见有无显著性统计学差异。强直性高频刺激海马诱发电位的幅值比较,AD模型组低于对照组(P0.01),西红花苷各剂量组高于AD模型组(P0.05),且西红花苷中、高剂量组高于低剂量组(P0.05)。西红花苷各剂量组海马GAP-43表达低于对照组(P0.01),高于AD模型组(P0.01)。结论:西红花苷对AD大鼠学习记忆能力有一定改善作用,增强海马LTP和GAP-43的表达。     

肉苁蓉总苷对兔失血性休克/再灌注损伤时脂质过氧化的影响

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电针对AD模型幼鼠学习记忆功能和海马突触可塑性的影响

目的：研究电针刺激“百会”“风府”和双侧“肾俞”对阿尔茨海默病（AD）模型幼鼠海马区突触可塑性的影响。方法：24只6周龄雄性APP/PS1转基因小鼠作为AD幼鼠模型,随机分为电针穴位组和AD模型组,每组12只;12只同月龄C57BL/6J小鼠作为正常对照组。电针刺激“百会”“风府”和双侧“肾俞”穴位,每天1次,每次20 min,每周休息1 d,连续干预16周。Morris水迷宫检测各组小鼠的学习记忆功能;Golgi染色检测海马CA1区树突棘数量;透射电镜观察海马CA1区神经元突触结构;实时荧光定量PCR和Western blot分别检测海马脑源性神经营养因子（BDNF）、突触小泡蛋白（SYN）和N-甲基-D-天冬氨酸受体2B亚基（NR2B）的mRNA和蛋白表达水平。结果：与正常对照组比较,AD模型组小鼠学习记忆功能明显下降;海马神经元树突棘部分丢失,数目减少（P<0.05）;海马区突触数量减少,结构模糊不清;海马BDNF、SYN和NR2B的mRNA和蛋白表达水平均显著降低（P<0.01或P<0.05）。与AD模型组比较,电针穴位组小鼠学习记忆功能明显增强;海马神经元树...     

雷公藤内酯醇对阿尔茨海默病模型大鼠海马突触素表达及突触超微结构的影响

目的:探讨雷公藤内酯醇对阿尔茨海默病模型大鼠海马突触素表达及突触超微结构的影响.方法:大鼠随机分成对照组、模型组、治疗组.模型组给予双侧海马各一次性注射凝聚态Aβ1-4010μg,治疗组在海马注射凝聚态Aβ1-40后,每日腹腔注射雷公藤内酯醇0 4mg/kg, 15d后用免疫组织化学方法和蛋白免疫印迹技术检测海马突触素表达情况,透射电镜观察突触结构的变化.结果:与模型组相比,治疗组海马区突触素免疫反应阳性产物数量(152 80±15 76)及平均光密度(0 3180±0 0278)均增加;突触素表达总量(1917 71±41 02)及密度比值(0 87±0 03)亦增加;突触结构较清晰,界面增长,突触后电子致密物增厚.结论:雷公藤内酯醇可以增加阿尔茨海默病模型大鼠海马突触素的表达,减轻阿尔茨海默病模型大鼠海马突触损伤程度.     

游泳运动对早期阿尔茨海默模型小鼠认知功能及海马突触可塑性的影响

目的评估游泳运动对早期阿尔茨海默模型小鼠认知功能及海马突触可塑性的影响。方法选取4～5月龄C57BL/6雄性小鼠和3xTg(APP/Tau/PS1三转基因)雄性小鼠各20只,分为4组(n=10),野生对照组(WT+C),野生游泳组(WT+S),3xTg对照组(Tg+C),3xTg游泳组(Tg+S)。对照组常规饲养,游泳组每日训练2次,每次10min,训练周期30日。利用经典Morris水迷宫实验(MWM)和旷场实验评估小鼠行为学差异,利用长时程增强(LTP)评估海马突触可塑性。结果 Tg+S组小鼠逃避潜伏期显著低于Tg+C组,在平台所在象限停留时间和移动距离显著高于Tg+C组;Tg+S组在高频刺激后30min内fEPSP的斜率显著高于Tg+C组。WT+C组和WT+S组在高频刺激后30min内fEPSP的斜率无显著差异(P0.05)。结论游泳运动改善早期阿尔茨海默模型小鼠的学习记忆能力和探索能力,与提高海马突触可塑性相关。     

雌激素对阿尔茨海默病模型大鼠学习记忆的影响

目的:探讨雌激素对阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠学习记忆能力的影响。方法:选取雌性SD大鼠24只,随机分为假手术组、卵巢切除组(ovariectomy,OVX)、OVX+苯甲酸雌二醇组(estradiolbenzoate,EB),每组8只。于海马注射Aβ1-42建立AD大鼠模型,通过Morris水迷宫观察大鼠的学习记忆能力,同时用ELISA检测脑组织超氧化物歧化酶(super oxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、乙酰胆碱酯酶(acetylcholine esterase,ACh E)的活性,用免疫组化分析神经元型一氧化氮合酶(n NOS)并测定其OD值。结果:与OVX组比较,OVX+EB组逃避潜伏期明显缩短(P0.05),原平台象限活动时间明显增加(P0.05),穿越原平台次数明显增多(P0.05)。雌激素作用还提高大鼠脑组织SOD、ACh E和n NOS活性,降低MDA活性(P0.05)。结论:研究表明雌激素可改善AD模型大鼠的学习记忆能力,其机制可能通过提高脑组织SOD、ACh E和n NOS活性,降低MDA活性有关。     

三七总苷对大鼠自身免疫性睾丸炎的拮抗作用

目的:研究三七总苷(PNS)对自身免疫性睾丸炎模型鼠睾丸组织形态及血清肿瘤坏死因子α(TNF-α)和睾酮(T)含量的影响,以探讨PNS对睾丸炎的组织结构拮抗及作用机制。方法:建立大鼠睾丸炎模型,随机分为模型组和PNS拮抗组(200、400和800mg/kg),镜下观察各组睾丸组织结构变化。结果:800mg/kg PNS剂量组睾丸系数、生精小管直径、血清TNF-α和T含量与模型组比较,差异有统计学意义,光镜所见睾丸组织结构接近正常对照组形态;200mg/kg PNS剂量组和模型组生精上皮坏死、脱落,睾丸间质水肿,不同程度炎性细胞增生浸润。结论:400、800mg/kg PNS剂量组对大鼠睾丸炎症损伤具有拮抗作用。     

三七总皂甙对大鼠脑出血后神经可塑性的影响

目的:探讨三七总皂甙对大鼠脑出血后神经可塑性的影响。方法:制作脑出血模型;将120只大鼠随机分成假手术组、模型组、三七总皂甙治疗组;免疫组化检测Nestin、Shank1表达;电镜观察突触超微结构并定量分析;对大鼠进行神经功能评分。结果:假手术组超微结构正常,模型组神经突触及细胞器溶解破坏,治疗组突触结构趋于正常,与模型组比较突触数量、界面曲率及突触后致密区均增大,突触间隙变窄,差异有统计学意义(P0.01)。与模型组比较,治疗组Shank1及Nestin蛋白阳性表达升高,差异有统计学意义(P0.01)。假手术组神经功能基本正常;模型组评分升高;与模型组比较,治疗组评分降低,差异有统计学意义(P0.01)。结论:三七总皂甙可增强神经可塑性,保护大鼠神经功能。     

红景天苷对血管性痴呆大鼠认知功能障碍的治疗作用

目的:探讨红景天苷(Sal)对血管性痴呆(VD)大鼠认知功能障碍的治疗作用,并从抑制氧化应激、改善线粒体功能等方面研究其可能机制.方法:选用57只健康雄性SD大鼠随机等分为假手术组(sham)、双侧颈总动脉结扎组(2-VO)和红景天苷治疗组(Sal),采用双侧颈总动脉结扎法复制2-VO模型.采用Morris水迷宫实验检...     

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Aβ) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD.     

Chronically increased oxidative stress in fibroblasts from Alzheimer's disease patients causes early senescence and renders resistance to apoptosis by oxidative stress

It is well established that oxidative stress is involved in several neurodegenerative disorders, including Alzheimer's disease (AD). Study of the induction and consequences of oxidative stress in the peripheral tissues of the familial AD patients can help to elucidate the inherent abnormalities and the mechanism of pathogenesis of this disease. AD fibroblasts have been used as a model to investigate the underlying mechanisms of oxidative stress. In our study, we used AD fibroblasts from six different donors who are either at high risk of developing AD or have already been diagnosed with AD to study the effect of oxidative stress in comparison with the effect on non-AD normal human fibroblast. Oxidative stress was induced by a brief exposure of the cells to 250microM H(2)O(2) followed by incubation in normal conditions. Neuronal loss due to oxidative stress is a characteristic of Alzheimer's patients; however, our results showed that AD fibroblasts were more resistant to oxidative stress compared to non-AD fibroblasts. Measurement of reactive oxygen species (ROS) indicated that AD fibroblasts produced more ROS than did non-AD NHF cells either in basal conditions or after induction of oxidative stress. Furthermore, we found that expression of p21 was significantly higher in AD cells than in non-AD cells and expression of Bax, a pro-apoptotic protein was downregulated/absent in AD cells during normal or under conditions of external oxidative stress. Further experiments revealed that mitochondria in AD cells moved to the peri-nuclear region following induction of oxidative stress. Thus, these results suggest that AD fibroblasts are chronically exposed to oxidative stress that may trigger senescent phenotype, making AD cell resistant to apoptosis by external oxidative stress.     

神经干细胞移植对痴呆大鼠记忆功能及海马组织氧化应激的影响

目的 研究神经干细胞移植对β淀粉样蛋白(Aβ1-40)所致痴呆大鼠记忆功能及海马组织丙二醛(MDA)、超氧化物岐化酶(SOD)的影响.方法 取新生大鼠脑皮质进行神经干细胞的分离、培养、鉴定,传代培养2-3代;选取30只健康SD大鼠随机分为3组,10只,组.对照组:侧脑室注入蒸馏水5μl;模型组:侧脑室注入Aβ1-40 ...     

Daytime sleepiness in mild and moderate Alzheimer's disease and its relationship with cognitive impairment

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n=11) and moderate (CDR2; n=9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques.     

Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimer's disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimer's disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.     

Effects of demographic factors on cortical thickness in Alzheimer's disease

The aim of this study was to investigate the effect of demographic factors (age of onset, sex and years of education) on the distribution of cortical thickness in a large sample of patients with Alzheimer's disease (AD). The study participants consisted of 193 AD patients and 142 controls with no cognitive impairment (NCI) that were measured with cortical thickness across the entire brain. The effects of demographic factors on cortical thickness were analyzed by applying linear regression after controlling confounding factors. Older individuals in NCI group showed more cortical thinning in frontal, temporal association cortices and insula than younger participants. Early onset AD was associated with cortical thinning in the parietal lobe, whereas late onset AD was associated with cortical thinning in the medial temporal region. The NCI group demonstrated sex-related differences in cortical thickness, although those differences were not present in the AD group. While the education effect was absent in NCI individuals, high levels of education in the AD group correlated with cortical thinning in the frontal and temporoparietal association cortices. Our results show that AD with earlier onset and higher education had suffered more pronounced cortical atrophy in specific parts of the brain than their counterparts, which may be related to cognitive reserve theory.     

Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease

Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimer's disease (AD). The cognitive change in AD has been correlated to the characteristic pathologic lesions in the brain, senile plaques (SP) and neurofibrillary tangles. Senile plaques are the most consistent correlative marker in AD. We present preliminary data indicating that abundant SP are found in the brains of nondemented patients dying with or as a result of critical coronary artery disease (cCAD) compared to nonheart disease (non-HD) subjects; 15 of 20 cCAD patients contained SP and only two of 16 non-HD patients contained SP.     

人参皂甙对Alzheimer病模型大鼠海马生长抑素mRNA表达的影响

目的：研究人参皂甙（GS）对Alzheimer病（AD）模型大鼠海马内生长抑素（SS）mRNA表达的影响。方法：本实验以D-半乳糖致衰老合并鹅膏蕈氨酸脑内Meynert核注射建立AD大鼠模型,运用原位杂交方法结合图像分析检测各组大鼠海马SSmRNA表达。结果：模型组大鼠海马各区SSmRNA表达阳性神经元平均灰度值比正常对照组明显升高,平均密度显著降低;而预防组、治疗组阳性神经元灰度值则比模型组显著降低,平均密度明显升高;正常对照组与人参皂甙对照组大鼠的CA4及DG区中,此两项指标差异显著。结论：GS对AD模型大鼠海马SSmRNA表达减弱有预防及治疗作用。     

小RNA与阿尔茨海默病发病机制研究进展

小RNA(miRNA)是一类非编码的小RNA,通过转录后水平调控细胞蛋白质的表达,在神经系统的生长发育、分化及功能执行中发挥重要的作用.脑组织内miRNA的异常表达可通过多种途径影响阿尔茨海默病的发生和发展.对于miRNA的研究将有助于深入了解阿尔茨海默病的发病机制.