丙戊酸钠对APP/PS1双重转基因AD模型小鼠脑内老年斑和神经元的影响

目的 探讨丙戊酸钠 (valproic acid sodium salt,VPA)处理对淀粉样蛋白前体蛋白(β-amyloid precursor protein,APP)/早老素1(presenilin1,PS1)双重转基因阿尔茨海默病(Alzheimer's disease,AD)模型小鼠是否发挥神经保护作用.方法 对APP/PS1双重转基因AD模型种鼠交配后产下的子代进行基因分型,运用VPA 30 mg/(kg·d)和等量生理盐水腹腔注射APP/PS1双重转基因小鼠4周.药物处理后采用免疫组化、甲硫素S染色检测VPA对老年斑(senile plapues,SP)的影响,用Nissl染色、Tunel染色观察脑内神经元的变化,并采用ELISA定量检测小鼠脑内β-淀粉样蛋白(amyloid β peptide,Aβ)水平.结果 免疫组化及甲硫素S染色结果显示:VPA治疗组较生理盐水组的小鼠大脑皮质及海马区域的老年斑数量明显减少(t ＝ 7.78,P ＜ 0.01).Nissl染色发现VPA治疗组小鼠皮质及海马内的神经元数目较生理盐水组增加;Tunel染色显示VPA治疗组小鼠脑内凋亡神经元明显减少(t ＝ 5.95,P ＜ 0.01);ELISA结果提示VPA治疗组小鼠脑内Aβ40(t ＝ 4.23,P ＜ 0.01)和Aβ42(t ＝ 7.51,P ＜ 0.01)水平显著低于对照组.结论 VPA处理能显著减少AD模型小鼠减少脑内Aβ的沉积和老年斑的形成,通过减少神经元的凋亡来增加神经元的数量.     

常压高氧对淀粉样蛋白前体/早老素1双重转基因小鼠脑内老年斑及β-淀粉样蛋白的影响

目的 探讨常压高氧(40%O_2,60%空气)处理淀粉样蛋白前体/早老素1(APP/PS1)双重转基因小鼠是否发挥神经保护作用.方法 对APP/PS1双重转基因阿尔茨海默病(AD)模型种鼠交配后产下的子代小鼠进行基因分型,待子代达10周龄时,取双重转基因小鼠40只,随机分成A、B、C、D 4组,每组10只,A、B 2组小鼠喂养于常压高氧中8 h/d,A组持续4周,B组持续8周;C、D组喂养于空气中4或8周,分别作为A、B组的对照.高氧处理后采用免疫组织化学、Thioflavin S染色检测小鼠脑组织形态学的变化,Western blot检测APP代谢过程中相关蛋白的表达变化,ELISA定量检测小鼠脑内β-淀粉样蛋白(Aβ)水平的变化.结果 免疫组织化学和Thioflavin S染色均显示,与对照组相比,高氧处理组小鼠皮质和海马内老年斑数量明显减少,B组比A组减少更显著.高氧处理组小鼠脑内C_(99)、C_(83)水平显著高于对照组,Aβ水平明显低于对照组,但各组小鼠脑内全长APP及β位淀粉样前体蛋白裂解酶1(BACE1)蛋白水平无明显改变.ELISA结果提示,B组小鼠海马和皮质内Aβ_(40)[(783.6±97.2)pg/ml]和Aβ_(42)[(175.3±17.1)ps/ml]含量明显低于对照组Aβ_(40)[(1251.6±42.3)pg/ml,t=9.36,P<0.01]和Aβ_(42)[(286.8±13.0)pg/ml,t=13.7,P<0.01]的含量.结论 常压高氧处理能显著减少AD模型小鼠脑内Aβ的产生、沉积及老年斑的形成;这种改变可能通过减少Aβ产生或加速Aβ清除实现.     

自噬及Rab9在阿尔茨海默病神经元变性过程中的作用

目的以12月龄的APPswe/PS1d E9双转基因小鼠为对象,研究自噬及Rab9在阿尔茨海默病神经元变性过程中的作用。方法以同窝同龄同性别野生型小鼠脑组织为对照,采用免疫荧光检测12月龄APPswe/PS1d E9转基因小鼠脑组织中Aβ1-16、LC3B和Rab9的表达;采用Western Blot对脑组织中LC3B-Ⅰ、LC3B-Ⅱ和Rab9蛋白表达进行定量分析。结果 12月龄APPswe/PS1d E9双转基因小鼠的皮质及海马区域有大量典型"有致密核心"的老年斑分布。12月龄的APPswe/PS1 d E9双转基因小鼠脑内LC3 B和LC3 B-Ⅱ的表达较对照组明显增多,差异具有统计学意义(LC3 B:0.819±0.034 vs.0.390±0.047,P=0.0005;LC3 B-Ⅱ:0.162±0.004 vs.0.067±0.001,P0.0001)。12月龄的APPswe/PS1 d E9双转基因小鼠脑内Rab9呈粗颗粒状,聚集为"半月形",分布于核周区,与在对照组小鼠脑内分布的形态不同;但两组在Rab9表达水平上差异无统计学意义(0.481±0.071 vs.0.508±0.064,P0.05)。结论阿尔茨海默病神经元变性过程中存在自噬诱导的增加和Rab9的功能和/或分布异常。     

雄性APP/PS1/Tau三转基因小鼠阿尔茨海默病样病理的年龄相关性变化

目的 用免疫组化(Immunohistochemistry,IHC)方法观察2～15月龄雄性APP/PS1/Tau三转基因小鼠(Triple transgenic mice,3xTg),每两月龄,海马及感觉皮质中阿尔茨海默病(Alzheimer disease,AD)相关病理的年龄相关性变化。方法 雄性3xTg-AD三转基因小鼠按2、4、6、8、10、12、15月龄分为7组,每组各3只,作为实验组;雄性C5B7L/6J小鼠(Wild Type,WT)按2、4、6、8、10、12、15月龄分为7组,每组各3只,作为对照组。用免疫组化法方法检测各个小鼠脑组织海马及感觉皮质与阿尔茨海默病密切相关的病理年龄相关性变化:Aβ、磷酸化tau、人tau P301L突变体的转基因产物、星形胶质细胞增生、神经元标记物。结果 与C5B7L/6J小鼠相比,APP/PS1/Tau三转基因小鼠Aβ细胞(6E10)、p-tau(AT8,Ser202/Thr205)、tau(HT7)星形胶质细胞(GFAP)免疫染色强度显著增强,P 0. 0001; 2～15月龄雄性APP/PS1/Tau三转基因小鼠海马及感觉皮质均未出现明显淀粉样斑块沉积,海马CA1区Aβ细胞(6E10) 8月龄开始染色程度逐渐增强,感觉皮质区染色程度保持不变,P 0. 05; CA1区tau(HT7) 2～6月龄染色程度较弱,6～15月龄染色程度保持稳定,感觉皮质区2～4月龄染色程度升高,4～15月龄染色程度保持稳定,P 0. 05; CA1区p-tau(AT8,Ser202/Thr205) 6月龄磷酸化程度开始升高,感觉皮质区12月龄磷酸化程度开始升高,P 0. 05; CA1区及感觉皮质区星形胶质细胞(GFAP) 2～15月龄反应性逐渐增强; CA1区成熟神经元标记物(NEUN)数量2～6月龄逐渐减少,6～15月龄稳定,CA3区NEUN数量2～15月龄逐渐降低,P 0. 05。结论 3xTg-AD小鼠在年龄和表型的发展之间显示出明显的相互作用,这使其成为研究衰老在疾病发病机制中作用的重要工具。     

侧脑室注射Noggin对AD小鼠海马神经发生和学习记忆功能的影响

目的观察侧脑室给予Noggin对AD小鼠海马神经发生和学习记忆功能的影响。方法选取12月龄APP/PS1双转基因AD小鼠,实验组连续7d侧脑室注射Noggin,对照组向侧脑室注射等量生理盐水,Morris水迷宫检测其认知功能,免疫荧光检测海马齿回BrdU的表达。结果和生理盐水对照组相比,侧脑室注射Noggin组小鼠海马齿回BrdU阳性细胞数显著增加(P0.01),行为学检测显示逃逸潜伏期缩短、穿过原平台位置次数和在原平台象限探索时间百分率增加(P0.05)。结论侧脑室注射Noggin可促进AD小鼠海马神经发生并改善其学习记忆能力。     

伴有和不伴有抑郁的阿尔茨海默病患者在静音Stroop任务下脑功能激活的差异

目的 研究Alzheimer病(AD)与AD伴抑郁患者(depression in Alzheimer's disease,dAD)在注意任务下脑功能激活区的差异.方法 收集临床诊断轻度AD患者20例,符合《精神疾病诊断与统计手册第Ⅳ版》标准(DSM-Ⅳ),其临床痴呆评定量表(CDR)评分1.0,其中9例dAD患者符合国立精神疾病研究院制定的痴呆伴抑郁的诊断标准(NIMH-dAD标准),其康奈尔痴呆中抑郁量表评分(CSDD)＞12.另有10名健康老龄者为对照组.在静音Stroop任务下,计算完成任务的反应时间、错误率和漏报率等行为学指标,同时采集fMRI脑部功能图像,使用SPM2软件分析.结果 dAD、AD与对照组的反应时间(ms)分别为2214.4±107.1、2020.6±558.3、840.0±254.5,dAD与AD组均明显慢于对照组(P＜0.01),且dAD组比AD组更慢(P=0.04).dAD、AD、对照组的错误率分别为:8.3%、6.9%、0.7%;其漏报率分别为:3.6%、2.9%、0,虽然dAD与AD组在错误率(P=0.13)和漏报率(P=0.10)间并无差异,但均明显高于对照组(P＜0.01).对照组在双侧前额背外侧皮质、双侧前扣带回、右侧顶叶和左额下回有明显的激活.AD组仅在左侧顶叶、左前扣带回和右额叶背外侧皮质等有少量激活.dAD组仅在前额皮质和部分右侧前额背外侧皮质处有少量激活.结论 与对照组相比,AD伴有和不伴抑郁的患者均存在异常的脑功能成像,但二者间有着明显的差别,抑郁加重AD的注意功能损害.     

姜黄素对AD小鼠海马神经元凋亡和GSK-3β表达及磷酸化的影响

目的观察姜黄素对AD小鼠模型海马神经元凋亡和糖原合成酶激酶3β表达及其磷酸化影响。方法将20只APP/PS1转基因小鼠随机分为AD模型组、AD模型+姜黄素组,每组10只,AD模型+姜黄素组腹腔注射剂量为400mg/(kg·d)姜黄素,1次/d,连续14d。取12只正常小鼠作对照组。采用扫描电镜检测小鼠海马神经元凋亡,Western blot检测GSK-3β、酪氨酸磷酸化GSK-3β(pTyr-GSK-3β)和丝氨酸磷酸化GSK-3β(pSer-GSK-3β)的表达情况。结果与对照组相比,模型组海马神经元出现染色质边集、线粒体肿胀、细胞器减少;pTyr-GSK-3β和pSer-GSK-3β的表达明显增加(t=5.112,P=0.005;t=5.619,P=0.006)。与模型组相比,姜黄素组海马神经元染色质呈弥散分布、线粒体嵴清晰可见、细胞器排列紧密,pTyr-GSK-3β表达明显降低(t=-7.985,P=0.001),pSer-GSK-3β表达明显提高(t=9.105,P=0.001)。结论 GSK-3β可能参与AD小鼠海马神经元损伤,姜黄素通过减少pTyr-GSK-3β、增加pSer-GSK-3β的表达抑制GSK-3β活性来减少AD小鼠海马神经元凋亡。     

EAAT2过表达对匹鲁卡品诱导小鼠癫痫持续状态模型的保护作用

目的 研究兴奋性氨基酸转运体2(EAAT2)过表达对癫痫发作及SE诱导的海马神经元死亡的作用.方法 实验采用野生型或者EAAT2转基因FVB/N小鼠,腹腔注射匹鲁卡品诱导癫痫持续状态(SE).SE后3 d,取脑、固定、切片,进行EAAT2、生长抑素的免疫组化染色以及甲酚紫染色,分别对海马CA1和齿状回门区阳性神经元进行计数.结果 与野生型动物相比,EAAT2在转基因小鼠海马中表达显著增加.野生型小鼠达到SE或者死亡所需的总匹鲁卡品剂量为344±40.3mg/kg,,而EAAT2转基因小鼠达到同等效应所需剂量为657±119.9 mg/kg,显著高于野生型所用剂量(P＜0.05).SE后3 d,野生型小鼠海马CA1区锥体细胞层神经元相对数量为0.56,而转基因动物中为0.9,显著高于野生型动物(P＜0.05).同时,野生型和转基因小鼠癫痫后齿状回门区中间神经元相对数量分别为0.11和0.67,转基因组数量显著高于野生型组(P＜0.05).野生型小鼠癫痫后齿状回门区生长抑素阳性神经元数量为0,但是,在EAAT2转基因小鼠,数量为0.4,显著高于野生型(P＜0.05).结论 EAAT2过表达对SE产生及其诱导的神经元死亡具有显著保护作用.过表达的EAAT2可能通过加强细胞外谷氨酸转运而调控其兴奋毒性.     

侧脑室注射p75~(NTR-ECD)对AD小鼠海马DCX表达与认知功能的影响

目的研究侧脑室注射p75NTR胞外段(extracellular domain of p75NTR,p75NTR-ECD)阻断内源性p75NTR对阿尔茨海默病(Alzheimer's disease,AD)小鼠海马神经发生和认知功能的影响。方法选取12月龄APP/PS1双转基因AD小鼠,实验组连续7d侧脑室注射p75NTR-ECD(1μg/d),对照组向侧脑室注射等量生理盐水,空白对照组未予处置,Morris水迷宫检测其认知功能,免疫组化检测海马齿回Doublecortin(DCX)的表达变化。结果与生理盐水对照组及空白对照组相比,侧脑室注射p75NTR-ECD组小鼠海马齿回DCX阳性细胞数显著增加(P0.01),行为学检测显示逃逸潜伏期缩短、穿过原平台位置次数和在原平台象限探索时间百分率增加(P0.05),生理盐水注射组和空白对照组DCX阳性细胞数及行为学检测显示差异无统计学意义(P0.05)。结论 p75NTR-ECD可促进AD小鼠海马神经发生并改善AD小鼠认知功能。     

Dab2调控阿尔茨海默病小鼠模型海马内TGF-β1/SMADs信号传导并减轻其脑损伤

目的研究Dab2蛋白对阿尔茨海默病疾病模型中TGF-β1/SMADs信号通路的调节作用以及其对阿尔茨海默病小鼠脑损伤的影响。方法 24只APP/PS1双转基因小鼠随机分为AD组、Vector组和Dab2组,每组8只,并将10只阴性对照小鼠作为对照组(Control)。对照组不做任何处理;饲养1个月后,AD组小鼠经双侧海马注射生理盐水,Dab2组小鼠双侧海马注射Dab2腺相关病毒质粒,Vector组小鼠双侧海马注射阴性对照质粒。所有小鼠于鼠龄9个月时进行行为学检测。10月龄时处死ELISA法检测脑组织中Aβ含量;Western blot检测海马中Dab2、TβRII和p-SMAD2/3的表达。结果 Dab2腺相关病毒质粒可在小鼠海马内高效表达Dab2。Dab2组小鼠海马组织中TβRII、p-SMAD2和p-SMAD3含量明显高于其阴性对照Vector组。Dab2组小鼠海马内Aβ含量明显低于Vector组,并且行为学评分明显高于Vector组小鼠。结论 Dab2过表达可通过上调TGF-β1/SMADs信号通路的传导,减轻阿尔茨海默病小鼠海马内Aβ的含量并改善其神经功能。     

孕期酒精暴露对子代大鼠学习记忆及海马N-甲基-D-天冬氨酸受体2B亚基表达的影响

目的 研究孕期酒精暴露对子代大鼠学习记忆及海马N-甲基-D-天冬氨酸(NMDA)受体2B亚基(NR2B)表达的影响.方法 按照随机数字表法,将雌性SD大鼠随机分为正常对照组、饮酒对照组和孕期酒精暴露组,每组各8只;饮酒法建立大鼠孕期酒精暴露模型,子代成年后,采用Y-型迷宫测试子鼠学习记忆成绩;采用聚合酶链反应分析子鼠海马组织NR2B mRNA的表达;采用免疫荧光法检测子鼠海马区NR2B蛋白表达.结果 (1)各组子鼠成年后学习记忆成绩的差异有统计学意义(F=4.566,P＜0.05),孕期酒精暴露组子鼠学习记忆成绩[(43.00±15.33)次]比正常对照组[ (25.13±12.35)次]和饮酒对照组[(26.12±11.95)次]明显下降(P均＜0.05);(2)各组子鼠成年后海马组织中NR2B mRNA表达差异有统计学意义(F=29.795,P＜0.01),孕期酒精暴露组子鼠海马区NR2B mRNA表达(0.97±0.14)较正常对照组(0.52±0.10)和饮酒对照组(0.62±0.12)明显上升(P均＜0.01);孕期酒精暴露组子鼠海马区NR2B蛋白表达明显增加.结论 孕期酒精暴露对子代大鼠的神经损伤可能与NMDA受体亚基NR2B蛋白表达的上调有关.     

SMAD6在Aβ诱导的神经毒性病变中的表达变化

目的探讨母抗Dpp小同源物6(small mothers against decapentaplegic homolog 6,SMAD6)在β淀粉样蛋白(amyloidβ,Aβ)诱导的神经毒性病变中的表达变化。方法取孕15~17d的SD大鼠的胎鼠,进行海马神经元原代培养,经不同浓度(10、15、20μmol/L)Aβ25-35毒性片段处理后,通过定量PCR技术检测SMAD6mRNA表达水平。取2月龄SD雄性大鼠12只,随机分为Aβ注射组和空白对照组,每组6只。采用双侧基底前脑注射Aβ1-40建立大鼠痴呆模型,通过免疫组化及免疫印迹检测基底前脑及海马区SMAD6蛋白表达水平。结果不同浓度Aβ25-35处理组海马神经元内SMAD6mRNA表达均较对照组减少(F=602.1,P0.01)。免疫组化结果显示,与对照组比较,Aβ1-40注射组大鼠基底前脑区SMAD6蛋白表达减少(68103±1520比96036±1804;t=20.51,P0.01),而海马区其表达增多(96441±1852比55039±1528;t=29.87,P0.01);免疫印迹结果显示,与对照组比较,Aβ1-40注射组大鼠基底前脑区SMAD6蛋白表达减少(0.1042±0.0067比1.000±0.0986;t=15.69,P0.01),而海马区其表达增多(12.5525±2.6803比1.000±0.0135;t=7.465,P0.01)。结论 Aβ可直接下调神经元内SMAD6mRNA转录及表达,不同脑区内SMAD6蛋白表达可能受负反馈调节机制影响。     

Relationship between plaques, tangles, and dementia in Down syndrome

In patients with Down syndrome, senile plaques and neurofibrillary tangles accumulate in the cortex at an earlier age than in persons of normal karyotype. We studied 20 Down syndrome patients dying after age 30 (average age, 49); all had neocortical plaques and tangles, but only 3 of 20 had been demented. In 12 cases (average age, 53), tissue was available for quantitative study of plaque and tangle densities and estimation of cell loss in the hippocampus. Although at least 8 of these 12 cases had plaque and tangle densities comparable to those previously reported in demented old people, only 1 had dementia. The regional distribution of plaques and tangles in the hippocampus of these Down cases differed from the pattern in senile dementia. Although Alzheimer-like dementia occurs in Down disease, it is less prevalent than the plethoric plaques and tangles in the cortex.     

颈动脉粥样硬化斑块与脑梗死关系的高分辨磁共振研究

目的探讨高分辨磁共振(MRI)对颈动脉粥样硬化斑块与脑梗死关系的评估价值。方法选取驻马店市精神病医院2014-01—2016-01收治的32例经高分辨MRI检查证实的脑梗死患者为试验组,以同期我院体检的行MRI扫描的25例无脑梗死患者作对照(对照组),采用三维时间飞跃法(3D-TOF)、T1加权(T1WI)、T2加权(T2WI)及增强颈部血管成像等扫描序列,分析颈动脉斑块的成分、分型及其与脑梗死的关系。结果试验组有颈动脉粥样硬化斑块者30例(93.75%),无颈动脉粥样硬化斑块者2例(6.25%);对照组有颈动脉粥样硬化斑块者6例(24.00%),无颈动脉粥样硬化斑块者19例(76.00%);试验组颈动脉粥样硬化斑块的发生率明显高于对照组(P0.01)。试验组共发现60块颈动脉粥样硬化斑块,其中Ⅰ~Ⅱ型7块(11.67%),Ⅲ型8块(13.33%),Ⅳ~Ⅴ型19块(31.67%),Ⅵ型21块(35.00%),Ⅶ型2块(3.33%),Ⅷ型3块(5.00%);对照组共发现14块颈动脉粥样硬化斑块,以稳定性斑块为主,Ⅰ~Ⅱ型13块(92.86%),Ⅳ型1块(7.14%)。2组颈动脉不稳定斑块发生率比较差异有统计学意义(P0.05)。脑梗死患者颈总动脉、分叉处及颈内动脉3个部位的粥样硬化斑块分布情况差异无统计学意义(P0.05)。结论高分辨MRI可清晰显示颈动脉粥样斑块的内部成分,且颈动脉粥样硬化斑块与脑梗死的发生有密切的相关性,高分辨MRI可对脑梗死的发生风险作出预测,为临床防治脑梗死及疗效评价提供重要的影像学依据。     

综合心理行为干预对军事演习应激状态官兵心理健康和事件相关电位P300的影响

目的 探讨综合心理行为干预对军事演习应激状态下官兵心理健康和事件相关电位P300的影响.方法 以某部参加军事演习的127名官兵为研究对象,以班为单位按随机数字表法分为研究组(63例)和对照组(64例),研究组演习前进行6周的心理行为与太极拳训练等综合干预.干预前1 d(干预前)、军事演习后第2天(干预后)分别对2组进行症状自评量表(Symptom Checklist-90,SCL-90)评估和事件相关电位P300检测.结果 (1)心理健康指标比较:与干预前比较,研究组干预后躯体化、人际关系敏感、焦虑因子分均降低,对照组躯体化、人际关系敏感、恐怖因子分及SCL-90总分均升高(P均＜0.05);与对照组比较,干预前2组SCL-90总分及各项因子分差异均无统计学意义(P均＞0.05),干预后研究组躯体化、人际关系敏感、焦虑、恐怖因子分均低于对照组(P均＜0.05).(2)事件相关电位P300指标比较:与干预前比较,研究组干预后Cz与FPz点P300靶刺激P3波幅升高(q=3.45、3.46,P均＜0.05),FPz点非靶刺激P2潜伏期(167.8±23.5)ms,短于干预前[(188.3±25.2)ms;q=3.54,P＜0.05];对照组干预后FPz点靶刺激P3潜伏期长于干预前(q=3.64,P＜0.05);与对照组比较,干预前2组Cz、FPz点潜伏期及波幅的差异均无统计学意义(F检验,P均＞0.05);干预后研究组Cz与FPz点靶刺激P3和非靶刺激P2潜伏期均短于对照组(P均＜0.05),Cz与FPz点靶刺激P3和FPz点非靶刺激P2波幅均高于对照组(q=3.34、3.35、3.68,P均＜0.05).结论 综合心理行为干预能够改善军事演习应激条件下官兵的心理健康水平和部分电生理指标.

Abstract：

Objective To explore the effects of the comprehensive psychological behavior intervention on the mental health and event-related potentials ( ERPs ) of the servicemen under military exercise. Methods One hundred and twenty-seven servicemen who participated in the military exercise were randomly divided into two groups, named the study group ( n = 63 ) and the control group ( n = 64 ). The servicemen in the study group were given the comprehensive psychological behavior intervention for 6 weeks.They were assessed with the Symptom Checklist-90 ( SCL-90 ) and event-related potential P300( P300 ) preintervention and post-intervention. Results ( 1 )The factors of somatization, interpersonal sensitivity, and anxiety of SCL-90 were significantly decreased after intervention in study group ( P ＜ 0. 05 ). In the control group, the factors of somatization, interpersonal sensitivity, phobic anxiety and total score post-intervention were significantly increased after military exercise ( P ＜0. 05 ). Before intervention, the difference on SCL-90score between the study group and the control group was not significant ( P ＞ 0. 05 ). After intervention, the factors of somatization, interpersonal sensitivity, anxiety, phobic anxiety and total score in the study group were significantly lower than that of the control group ( P ＜0. 05 ). ( 2 )After intervention, the study group showed higher amplitude on target P3 of P300 at Cz and FPz than the baseline ( q = 3.45, 3.46, P ＜ 0. 05 ),and shortened latency on non-target P2 at FPz[( 167.8 ± 23.5 )ms vs. ( 188. 3 ± 25. 2 )ms,q =3.54,P ＜0. 05] . The control group showed higher latency on target P3 at FPz than baseline ( q = 3.64, P ＜ 0. 05 ).Before intervention, there was no significant difference with P300 between two groups ( P ＞0. 05 ). Compared with the controls after intervention, the study group manifested shorter latency on target P3 and non-target P2at Cz and FPz ( P ＜0. 05 ). And higher amplitude on target P3 at Cz and FPz and on non-target P2 at FPz were appeared ( q = 3.34, 3. 35, 3.68, P ＜ 0. 05 ). Conclusion The comprehensive psychological behavior intervention could effectively improve the mental health and partly electrophysiological index of the serviceman in military stress.     

Combined measurements of hippocampal N-acetyl-aspartate and T2 relaxation time in the evaluation of mesial temporal lobe epilepsy: correlation with clinical severity and memory performances.

PURPOSE: In this study we tried to find a correlation between the clinical severity and memory performances, by comparing proton magnetic resonance (MR) spectroscopy and T2 relaxation time measurements in the hippocampi, in a homogeneous group of 27 patients with unilateral mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis on MR imaging, with a view to answer the following questions: (a) how sensitive is this approach for the assessment of the apparently normal contralateral hippocampus, (b) do the results relate to the clinical severity, and (c) does it allow evaluation of the degree of hippocampal dysfunction. METHODS: Volume-selective proton MR spectroscopy of the head of both hippocampi was performed at 3 T, by using the PRESS sequence, with an echo time of 135 ms, to estimate NAA/(Cho + Cr) ratios. The relaxation times were measured at 0.28 T, by using a conventional Carr-Purcell-Meiboom-Gill sequence, with a repetition time of 2,000 ms, an echo time of 15 ms, and 48 echoes. RESULTS: The combination of NAA/(Cho + Cr) ratio and T2 relaxation time values was allowed to classify contralateral hippocampus abnormalities in two groups: first, decreased NAA/(Cho + Cr) ratio with strongly increased T2 relaxation time values corresponding to abnormalities observed in sclerotic ipsilateral hippocampi; and second, decreased NAA/(Cho + Cr) ratio with normal or slightly increased T2 relaxation time values. Whereas the NAA/(Cho + Cr) ratio or T2 relaxation time value alone was not correlated with memory performances, their association shows that left hippocampal injury evaluated both by NAA and T2 relaxation time measurements was clearly correlated with verbal memory scores, and right hippocampal injury, with visual memory scores. On the other hand, the maximal seizure frequency reported by the patients was correlated with ipsilateral NAA/(Cho + Cr) ratio and T2 relaxation time values but not with contralateral results. CONCLUSIONS: We showed that the combination of NAA and T2 relaxation time measurements can be used to examine the degree of ipsi- and contralateral hippocampal dysfunction or injuries and their relations with memory performances in the presurgical evaluation of patients.     

Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopathological evaluation of a 10-year autopsy population

To examine the neuropathological and clinical characteristics of cerebral aging, we evaluated retrospectively a non-selected autopsy population of 1258 patients from the Geriatric Hospital of the University of Geneva School of Medecine. The prevalence of Alzheimer's disease increased with age below 90 years of age. In the nonagenarians and centenarians, there was a decline in the number of affected cases. The distribution with age of neurofibrillary tangles and senile plaques varied among the cortical areas studied. The CA1 field of the hippocampus and the inferior temporal cortex displayed increasing densities of neurofibrillary tangles with age, whereas the superior frontal and the occipital cortex were relatively spared, especially in patients in their tenth and eleventh decade. The percentage of cases presenting with senile plaques in the neocortex and hippocampal structure increased with age with a marked predominance of cases with moderate to high senile plaque densities. Neurofibrillary tangles were often observed in the CA1 field and the inferior temporal cortex of non-demented individuals and were present in most cases with Alzheimer's disease. Conversely, the involvement of the superior frontal and occipital cortex was moderate even in demented patients. The distribution of senile plaques was homogeneous in all of the neocortical areas independently of the clinical diagnosis. Moreover, there was no correlation between the presence of heurofibrillary tangles and senile plaques in the cerebral regions studied. These results indicate a differential topography of neurofibrillary tangles and senile plaques, and suggest that overt clinical signs of Alzheimer's disease are linked to the progression of the neurodegenerative process in neocortical areas.Supported in part by grants from the NIH (AG05138) and the Brookdale Foundation (to P.R.H.)     

西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

目的 探讨西酞普兰对慢性应激大鼠海马CA1、CA3神经细胞B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl相关蛋白(Bax)表达和凋亡的影响.方法 40只雄性Sprague-Dawley大鼠随机分为对照组、应激组(生理盐水灌胃)、处理1～3组[分别以不同剂量(1 mg·kg-1·d-1、4 nag·kg-1·d-1、8 mg·kg-1·d-1)氢溴酸西酞普兰灌胃],每组8只.采用强迫游泳制造慢性应激模型,用大鼠悬尾实验、力竭实验进行行为学观察,免疫组织化学检测Bel-2、Bax表达水平.脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测细胞凋亡.尼康图像分析软件测量分析Bcl-2、Bax阳性表达、凋亡阳性细胞数量及积分吸光度值.结果 应激组静止不动时间[(279±53)s]长于对照组[(182±35)s]及处理1～3组[(200±71)s,(159±59)s,(165±54)s];挣扎次数[(20±3)次]少于对照组[(24±3)次]及处理1～3组[(37±16)次,(32±10)次,(24±4)次];力竭时间[(38.3±5.1)min]长于对照组[(22.9±1.8)min]、短于处理1～3组[(54.4±2.9)min,(69.3±17.6)min,(46.4±4.0)min];差异均有统计学意义(P<0.05或0.01).与对照组比较,应激组CA1、CA3神经细胞Bcl-2表达变弱、Bax表达增强、凋亡细胞增多,差异均有统计学意义(P<0.05或0.01).与应激组比较,处理1～3组Bcl-2表达增强、Bax表达变弱、凋亡细胞减少,差异均有统计学意义(P<0.05或0.01).处理组1～3组的部分Bcl-2/Bax表达、凋亡阳性细胞数量与对照组的差异有统计学意义(P<0.05),但IA值的差异均无统计学意义(P均>0.05).结论 慢性应激可影响大鼠海马CAI、CA3神经细胞Bcl-2、Bax表达水平,促进细胞凋亡;西酞普兰可影响慢性应激大鼠海马CAI、CA3神经细胞Bcl-2、Bax表达水平,拈抗细胞凋亡.     

脑缺血再灌注后少突胶质细胞转录因子Olig1、轴突生长抑制因子Nogo-A基因表达与白质损伤

目的 检测少突胶质细胞转录因子Olig1、轴突生长抑制因子Nogo-A在大鼠脑缺血再灌注后不同时间点基因表达的变化规律,观察白质损伤的病理变化,探讨两者之间的关系.方法 利用线栓法制备大鼠大脑中动脉缺血(middle cerebral artery occlusion,MCAO)再灌注模型,实时定量PCR方法(relative quantification PCR,RQ-PCR)检测各时间点Olig1、Nogo-A在大脑损伤白质区的基因表达,髓鞘快蓝-高碘酸雪夫(LFB-PAS)染色法标记大脑神经髓鞘,Bielschowsky银染法标记大脑神经轴突,并计算缺血侧与健侧髓鞘染色的积分吸光度(Ias)比值以代表白质受损程度.结果 (1)Olig1:Olig1在缺血再灌注不同时间点,在大脑白质区的基因表达量不同.缺血再灌注6 h Olig1表达量减低至假手术组的83%(与假手术组相比,q=2.074,P=0.042),7 d时表达量降至最低,14 d时恢复至基础水平,21 d时表达最升高至假手术组的1.52倍(与假手术组相比,q=6.362,P＜0.01,差异具有统计学意义).Nogo-A:Nogo-A在缺血再灌注不同时间点,在大脑白质区的基因表达量不同.Nogo-A 基因表达在缺血再灌注1 d时开始减低,表达量降至假手术组的84%(与假手术组相比,q=2.230,P=0.029),7 d时降至最低,14～21 d表达量开始上调,21 d时表达量上调至假手术组的66%(与假手术组相比,q=4.681,P＜0.01).(2)缺血再灌注不同时问点髓鞘染色Ias比值不同,再灌注6 h时开始下降(0.91±0.05),与假手术组(1.03 ±0.09)相比,q=3.829,P＜0.01;12 h时有空洞形成,再灌注14 d髓鞘损伤达到高峰,Ias比值降到最低(0.31±0.07),髓鞘脱失明显;21 d的髓鞘Ias比值(0.30±0.06)与14 d(0.31±0.07)相比较差异无统计学意义(q=0.257,P=0.798).轴突变化规律与髓鞘基本相同.结论 Olig1、Nogo-A在脑缺血再灌注损伤过程中呈现动态变化规律,并与白质损伤的变化规律基本相同,提示Olig1、Nogo-A可能参与了再灌注损伤的病理生理过程,并与缺血再灌注白质损伤及修复密切相关.