缺氧条件下梭曼中毒对大鼠脑M受体的影响

目的 探讨高原缺氧条件下梭曼中毒大鼠脑组织乙酰胆碱酯酶（ＡＣｈＥ）活性和毒蕈碱性乙酰胆碱（Ｍ）受体变化规律。方法 以ＤＴＮＢ法和受体放射性配基结合法检测大鼠皮层、海马及纹状体ＡＣｈＥ活性和Ｍ受体密度及亲和力。结果 缺氧使大鼠脑组织ＡＣｈＥ活性不同程度升高,缺氧２４ｈ海马和纹状体Ｍ受体 分别增加１０．４％和２５．３％,Ｍ受体的亲和力分别增加５５．６％和３０．３％。单纯梭曼中毒和缺氧复合梭曼中毒均显著     

老年大鼠脑M_1亚型受体的变化及黄芪的调节作用

目的：观察老年大鼠不同脑区胆碱能Ｍ１亚型受体的变化和黄芪对其的调节作用。方法：采用放射自显影技术显示大鼠脑Ｍ１受体，并用图像分析仪进行灰度分析，以反映Ｍ１受体在不同脑区的相对定量分布。结果：所得脑切片自显影灰度层次清晰，主要分布在大脑皮质、海马、纹状体部位，非特异结合灰度很低，老年大鼠皮质、海马、纹状体的灰度显著低于青年鼠，分别降低１５７８％，８６９％，１２３６％（Ｐ＜００５），老年服黄芪组三个部位的灰度均明显高于老年对照组，分别升高１６６３％，９８１％，１０３２％，（Ｐ＜００５）。结论：黄芪对老年大鼠降低的脑胆碱能Ｍ１亚型受体具有上调作用。     

SE大鼠认知、情感障碍与海马乙酰胆碱酯酶纤维分布改变的关系

目的 探讨实验性癫痫持续状态(status epilepsy,SE)对大鼠认知功能的影响及与乙酰胆碱酯酶(acetylcholinesterase,AChE)阳性神经纤维在脑部分布变化的关系.方法 戊四氮诱导大鼠SE,行为学检测大鼠情感反应和学习记忆功能的改变.组织化学的方法观察海马、皮层AChE纤维分布的改变.结果 SE可引发实验动物活动习性发生改变,警觉水平、恐惧、焦虑等防护性情感反应下降及空间学习和记忆能力受损,伴有海马、皮层分子层AChE阳性神经纤维密度减低.结论 SE使大鼠情感行为发生改变和学习记忆功能受损,可能与海马、皮层AChE阳性神经纤维减少有关.     

大鼠不同脑区基因组DNA的RAPD分子标记

目的比较3月龄SD大鼠不同脑区(皮层、海马、纹状体、下丘脑、小脑)基因组DNA多态性。方法RAPD—PCR技术分析脑DNA多态性图谱。结果脑不同区域RAPD标记不尽相同，即纹状体、下丘脑为1543、1269、994、472、377bp5条条带，海马仅377bp1条条带，皮层为1543、1269、994、472bp4条条带，小脑为1269、994、377bp3条条带。结论脑不同区域存在DNA多态性，这可能反映出大鼠不同脑区基因组DNA的差异。并构成各脑区保持相对独立功能的结构基础。     

PROTECTIVE EFFECT OF TETRAMETHYLPYRAZINE ON LEARNING AND MEMORY FUNCTION IN D-GALACTOSE-LESIONED MICE

ALZHEIMER'Sdisease(AD)isaneurodegenerative disorderofcentralnervoussystemthatcausespro-gressivecognitiveandmemorydysfunctionintheelderlypeople.ADbrainsarecharacterizedbythepresenceofsenileplaques(SP)andneurofibrillarytangles (NFT),ac-companiedbythedecreaseofacetylcholine(ACh)levelandAofnumberofcholinergicneuronsandsynapses.1,2 Withtheincreaseoftheelderlypeople,theincidenceofADisincreas-ingandgivingrisetoaheavyloadonfamiliesandsociety.ThoughalotofresearcheshavebeenmadeonAD,thepath-oge…     

放射自显影技术研究老年大鼠不同脑区M胆碱受体的变化

目的： 观察自然衰老大鼠不同脑区Ｍ 胆碱受体包括Ｍ１ 亚型受体的变化。方法： 采用放射自显影技术显示大鼠脑Ｍ 受体,并用图像分析仪进行灰度分析,以反映Ｍ 受体在不同脑区的相对定量分布。结果： 所得脑切片自显影灰度层次清晰,主要分布在大脑皮质,海马,纹状体等部位,非特异结合灰度很低,图像分析仪分别给出不同脑区的平均灰度值,老年鼠皮质,海马,纹状体部位的灰度显著低于青年鼠,Ｍ 受体分别降低２４８７ ％ ,１４１２ ％ ,１２７６ ％ （ Ｐ＜ ００５） ,Ｍ１ 亚型受体分别降低１５７８ ％ ,８６９ ％ ,１２３６ ％ （ Ｐ＜ ００１） 。结论： 以上３ 个重要脑区Ｍ 胆碱受体密度的改变可能是脑衰老的一个重要机制     

γ—氨基丁酸及其受体在大鼠纹状体边缘区的表达

目的：观察γ－氨基丁酸（GABA）及其受体GABARB1 mRNA在纹状体边缘区的表达，探讨GABA对边缘区学习记忆功能的调控。方法：应用免疫细胞化学方法观察GABA及其合成酶谷氨酸脱羧酶（GAD）在纹状体边缘区的分布，用分子原位杂交方法观察GABA受体GABARB1 mRNA在纹状体边缘区内的表达。结果：在纹状体边缘区内可见密集的GABA及GAD免疫阳性纤维及少量胞体，在皮层，海马等处也可见阳性纤维及胞体，边缘区内可见许多GABAR1 mRNA表达阳性的细胞，尾壳核内只有少量GABARB1 mRNA阳性细胞分布，皮层，海马等处也呈GABARB1 mRNA阳性表达。结论：证实边缘区存在着GABA及其受体的表达，表明存在着抑制性氨基酸对边缘区的调控，推测GABA通过抑制突触前递质的释放及调控其他神经递质来影响边缘区的学习记忆功能。     

葛根素对急性乙醇中毒大鼠脑内阿片肽和多巴胺的调控作用

目的： 检测葛根素对急性乙醇中毒大鼠皮层、小脑、海马和纹状体内阿片肽和多巴胺（DA）表达水平的调控作用,为临床防治乙醇中毒和开发中药葛根提供依据。方法： 雄性SD大鼠24只随机分为对照组、乙醇中毒组和葛根素组,每组8只,采用放射免疫法检测各组大鼠皮层、小脑、海马和纹状体内β-内啡肽（β-EP）、强啡肽（DnyA）和亮脑啡肽（L-EK）表达水平,采用高效液相色谱法检测各组大鼠各脑区DA、多巴克（DOPAC）和高香草酸（HVA）的表达水平,并计算（DOPAC+HVA）/DA的比值。结果：与对照组比较,乙醇中毒组和葛根素组大鼠皮层内β-EP、DnyA和L-EK表达水平降低(P<0.01),皮层、小脑、海马和纹状体内 DA、DOPAC和HVA表达水平均升高 (P<0.01);与乙醇中毒组比较,葛根素组大鼠皮层内β-EP、DnyA和L-EK表达水平升高(P<0.05,P<0.01),DA(P<0.01)、DOPAC(P<0.01)和HVA表达水平均降低,小脑、海马和纹状体内所有指标表达水平均降低(P<0.05,P<0.01),皮层、小脑和海马内（DOPAC+HVA）/DA 比值升高,纹状体内该比值降低（P>0.05）。结论：葛根素对急性乙醇中毒造成的脑组织损伤有保护作用,其机制可能与葛根素对脑内阿片肽和DA的调控有关。     

D-半乳糖衰老模型大鼠学习记忆能力和特定脑区抗氧化酶活性的变化

目的 探讨D-半乳糖衰老模型大鼠学习记忆能力和特定脑区抗氧化酶活性的变化,以揭示学习记忆能力与特定脑区抗氧化酶活性的关系.方法 Wistar大鼠皮下注射D-半乳糖建立衰老模型,在MG-2型三等分辐射式迷宫中进行学习记忆能力的检测后,将大鼠立即断头处死,分别测定大脑皮层、小脑、纹状体、海马、下丘脑五个脑区SOD、CAT、GSH-Px活性.结果 D-半乳糖衰老模型大鼠迷宫正确反应率为(58.9±5.4)%,比对照组的(66.8±8.9)%明显降低(P＜0.05).24h后达标次数显著高于对照组[衰老组(29.5±12.8)次,对照组(16.6±6.2)次,P＜0.01],24h正确反应率明显降低于对照组[衰老组(67.3±10.3)%,对照组(79.1±6.9)%,P＜0.01].与对照组比较:皮层、海马、纹状体SOD活性(衰老组:66.12±5.89、80.46±6.57、87.82±6.87;对照组:57.63±4.21、67.46±6.80、68.37±6.52)显著降低(P＜0.05和P＜0.01);CAT活性在皮层、海马、纹状体、下丘脑四个脑区(衰老组:6.45±0.55、5.86±0.35、6.93±0.63、8.89±0.38;对照组:5.32±0.56、4.76±0.38、4.37±0.43、6.11±0.37)均显著降低(P＜0.05和P＜0.01);各脑区GSH-Px活性差异无显著性(P＞0.05).结论 D-半乳糖衰老模型大鼠学习记忆能力降低.衰老过程中海马、皮层、纹状体、下丘脑的抗氧化酶活性变化与学习记忆密切相关.     

GSH脑保护作用及其吸收机制的研究

目的：研究口服GSH的脑保护作用并探讨其在肠道的吸收机制。方法：观察口服GSH对小鼠耐缺氧能力和对大鼠皮层、下丘脑、纹状体、脑干及海马的GSH、SOD及LPO的影响,以及Acivicin预处理大鼠后口服GSH,以上五个脑区GSH的变化。结果：口服GSH可明显提高小鼠耐缺氧能力;大鼠皮层、下丘脑、纹状体、脑干及海马GSH上升、LPO下降,在皮层、下丘脑、纹状体及脑干SOD活性升高;Acivicin预处理大鼠后,口服GSH仍能使大鼠下丘脑、纹状体及脑干GSH提高。结论：口服外源性GSH对脑组织有保护作用,其保护作用同脑内GSH含量提高、SOD活性升高和LPO下降有关;外源性GSH在肠道的吸收有整分子GSH吸收参与。     

LPL基因mRNA在精神分裂症模型大鼠脑组织中的表达

目的: 探讨脂蛋白酯酶(LPL)基因mRNA在精神分裂症模型大鼠前脑皮层、杏仁核、尾壳核和海马4个脑区中的表达,阐明其在精神分裂症发病中的作用机制。 方法: 选择围产期Wistar大鼠,模型组24只,对照组21只,建立苯环已哌啶(PCP)处理的大鼠精神分裂症动物模型,通过Morris水迷宫实验验证动物模型是否建立成功,并检测其认知改变,采用实时荧光定量PCR法检测LPL基因mRNA在精神分裂症模型大鼠前脑皮层、杏仁核、尾壳核和海马4个脑区中的表达。 结果: Morris水迷宫实验,与对照组比较,模型组大鼠找到平台的时间明显延长,为对照组的4.25倍(P<0.01);与对照组比较,模型组大鼠脑组织中前脑皮层和海马区LPL mRNA表达水平降低,分别下降了61.7%和89.0%(P<0.05)。 结论: LPL基因在大鼠前脑皮层和海马表达水平降低可能与精神分裂症有关联,并且可能与认知障碍存在一定的联系。     

γ-氨基丁酸及其受体在大鼠纹状体边缘区的表达

目的观察γ-氨基丁酸(GABA)及其受体GABARB1mRNA在纹状体边缘区的表达,探讨GABA对边缘区学习记忆功能的调控。方法应用免疫细胞化学方法观察GABA及其合成酶谷氨酸脱羧酶(GAD)在纹状体边缘区的分布。用分子原位杂交方法观察GABA受体GABARB1mRNA在纹状体边缘区内的表达。结果在纹状体边缘区内可见密集的GABA及GAD免疫阳性纤维及少量胞体,在皮层、海马等处也可见阳性纤维及胞体。边缘区内可见许多GABARB1mRNA表达阳性的细胞,尾壳核内只有少量GABARB1mRNA阳性细胞分布,皮层、海马等处也呈GABARB1mRNA阳性表达。结论证实边缘区存在着GABA及其受体的表达,表明存在着抑制性氨基酸对边缘区的调控,推测GABA通过抑制突触前递质的释放及调控其他神经递质来影响边缘区的学习记忆功能。     

大鼠纹状体边缘区和海马的功能联系研究

目的研究纹状体边缘区与具学习记忆功能的重要脑区———海马之间是否存在功能联系。方法用神经系功能活动形态定位法,将低浓度的海人藻酸作为化学刺激剂注射于大鼠海马,用免疫组化法观察c-fos原癌基因在脑内的表达。结果c-Fos 在海马、杏仁核、终纹床核、大脑皮层等部位有强烈表达;在纹状体中,c-Fos表达成条带状集中分布在边缘区,而在尾壳核和苍白球少有表达。结论海马与纹状体边缘区存在密切的功能联系。     

帕金森病大鼠脑局部葡萄糖代谢及多巴胺2型受体表达的microPET研究

目的 应用18F-FDG和11C-NMSP microPET评估大鼠帕金森病(PD)模型脑局部葡萄糖代谢及多巴胺2型受体(DRD2)表达的差别及意义.方法 采用6-羟多巴胺制备偏侧PD大鼠模型,2周后应用18F-FDG和11C-NMSPmicroPET扫描,比较PD模型组大鼠和对照组大鼠的脑局部葡萄糖代谢及DRD2表达,用免疫组化染色比较两组的酪氨酸羟化酶表达.结果 PD模型大鼠纹状体、海马、感觉运动皮质葡萄糖代谢率分别为88.2%±2.2%,94.5%±4.5%,96.2%±5.8%,显著低于对照组相应脑区92.7%±2.8%(P＜0.01),98.9%±3.9%(P＜0.01),102.8%±2.1%(P＜0.01);DRD2表达在PD模型的右侧纹状体为112.9%±9.0%,明显高于对照组102.3%±1.4%(P＜0.01).结论 PD模型大鼠损毁侧纹状体、海马、感觉运动皮质葡萄糖代谢均降低;而损毁侧纹状体DRD2表达明显升高.18F-FDG和11C-NMSP microPET能有效评估PD模型脑局部葡萄糖代谢及DRD2表达水平,可能成为早期诊断PD的分子影像学工具.

Abstract：

Objective To employ 18F-fluoro-2-aeoxyglucose (18 F-FDG) and (3-N-[11 C] methylspiperone ) 11C -NMSP microPET to assess the changes of regional cerebral glucose metabolism and the expression of dopamine receptor type 2 ( DRD2 ) in a rat model of Parkinson's disease (PD). Methods A hemiparkinsonian model was established in rats by unilateral pretreatment with 6-hydroxydopamine (6-OHDA). At 2 weeks after 6-OHDA insult, 18F-FDG and 11C-NMSP microPET scan were performed to compare the differences of regional cerebral glucose metabolism and the expression of DRD2 between the PD and control groups respectively. The immunohistochemical staining was used to detect the expression of tyrosine hydroxylase in two groups. Results In the PD model, the glucose metabolism rates were 88. 2% ± 2. 2%, 94. 5% ±4.5% and 96. 2% ±5. 8% respectively, in right striatum, hippocampus and sensorimotor cortex. And they were significantly lower than those in the control group [ 92. 7% ± 2. 8% ( P ＜ 0. 01 ),98.9% ±3.9% (P＜0.01) & 102.8% ±2. 1% (P＜0.01) ].The expression of DRD2 in right striatum was significantly higher in the PD group than that in the control group ( 112. 9% ± 9. 0% vs 102. 3% ± 1.4%, P ＜ 0. 01 ). Conclusion In the PD rats, glucose metabolism decreases in injured side striatum,hippocampus and sensorimotor cortex while and the expression of DRD2 increases in injured side striatum.18F-FDG and 11C-NMSP microPET can effectively assess the regional cerebral glucose metabolism and the expression of DRD2 in PD. They may serve as effective molecular imaging tools for an early diagnosis of PD.     

大鼠纹状体边缘区和海马的功能联系研究

目的：研究纹状边缘区与具学习记忆功能的重要脑区－海马之间是否存在功能联系。方法：用神经系功能活动形态定位法，将低浓度的海人藻酸作为化学刺激剂注射于大鼠海马，用免疫组化法观察c-fos原癌基因在脑内的表达，结果：c-Fos在海马，杏仁核，终纹床核，大脑皮层等部位有强烈表达，在纹状体中，c-fos表达成条带状集中分布在边缘区，而在尾壳核和苍白球少有表达。结论：海马与纹状体边缘区存在密切的功能联系。     

细胞周期相关因子P15在痴呆鼠脑不同部位表达及针刺的影响

目的 了解细胞周期蛋白依赖性激酶抑制因子(P15)在老年性痴呆(AD)模型快速老化模型小白鼠(SAMP8)不同脑区中的表达规律及针刺对其表达的影响.方法 15只10月龄快速老化模型小白鼠,随机分为正常组、模型组、针灸组,每组5只.用免疫组化法和病理图像分析技术测定P15在SAMP8皮层、海马、纹状体、嗅球等脑区中的阳性细胞数.结果 P15在正常组和SAMP8组中4个脑区的表达趋势一致,在嗅球区的表达明显高于其他3个脑区;P15在SAMP8的海马区表达增高、在嗅球及纹状体区表达低于正常组,差异有统计学意义.针刺能够下调SAMP8皮质、海马区的表达,且有统计学意义.结论 海马区细胞凋亡、嗅球和纹状体区细胞增殖可能是AD重要的病理改变,针刺可减少皮质、海马区的神经细胞凋亡,为针刺治疗AD的分子机制提供了新的内容.     

大鼠脑缺血再灌流脑区一氧化氮合酶的变化

研究大鼠脑缺血再灌注后大脑皮层,海马,纹状体和小脑组织一氧化氮合酶的变化。方法采用放射免疫法检测脑组织中ＮＯＳ的活性。结果大鼠脑缺血后５ｍｉｎ,各脑区结构型ＮＯＳ（ｃＮＯＳ）活性明显升高,持续到脑缺血３０ｍｉｎ,脑缺血３０－６０开始下降,诱导型ＮＯＳ（ｉＮＯＳ）活性在脑缺血后１０－１５ｍｉｎ开始升高,并持以脑缺血６０ｍｉｎ;脑缺血３０ｍｉｎ再灌注１５ｍｉｎ,各脑区ｃＮＯＳ和ｉＮＯＳ活性明显高于缺血     

老年早期及老年晚期大鼠脑胆碱能M型受体的改变

采用放射自显影技术测定脑切片胆碱能Ｍ型受体，观察大鼠在老年早期和老年晚期不同脑区Ｍ型受体密度的变化。结果：所得脑切片自显影像灰度层次清晰，主要分布在皮质、海马、纹状体等部位，非特异结合灰度很低。图像分析仪分别给出不同脑区的平均灰度值，老年鼠皮质、海马、纹状体的灰度显著低于青年鼠，老年早期大鼠３个脑区分别降低２４８７％，１４１２％，１２７６％（Ｐ＜００５）；老年晚期分别降低２９４５％，２４３３％，１５３１％（Ｐ＜００５）。结论：老年大鼠大脑皮质、海马、纹状体部位胆碱能Ｍ型受体密度显著降低，老年晚期比老年早期降低的幅度更大     

The effects of sex on brain iron status in rats

Objective:Iron plays essential roles in the human body.Studies have shown that iron is distributed differently in male and female Rats in liver,spleen,bone marrow,kidney,heart.However,the effects of sex on iron distribution in central nervous system are not well established.Methods:To explore the effects of the above mentioned,in this study,female and male Sprague Dawley rats were used at 4 months of age.The synthesis of ferritin light chain(FTL),transferrin receptor1(TfR1),ferroportin 1(FPN1),divalent metal transporter 1(DMT1)in the cortex,hippocampus,striatum,cerebellum,and olfactory bulb was determined by Western blot analysis.Results:The results showed that the levels of FTL protein in the cortex,hippocampus,striatum,cerebellum,and olfactory bulb were higher in female rats than in male rats,but the levels of TfR1 protein were lower in female rats than in male rats.There was no significant change in FPN1 and DMT1 expression in brain.Conclusions:These data suggest that sex have effects on brain iron status.Iron is distributed differently in central nervous system in male and female rats.However,the precise mechanisms need further study.     

Targeting PDE4 for Alzheimer’s Disease and Alcoholism: An implication in Alcohol-Related Dementia?

Background: Phosphodiesterase 4 (PDE4), one of the 11 PDE enzyme families that hydrolyze cyclic nucleotides, is critical for controlling intracellular cyclic AMP (cAMP) concentrations and plays an important role in regulating alcohol consumption and mediating memory in dementia such as Alzheimer’s disease (AD). Chronic alcohol consumption can cause alcohol-related dementia and 50-75% of detoxified alcoholics have memory or cognition impairment. However, the role of PDE4 and its mechanism remain to be characterized and elucidated. Methods: Using the water-maze, passive avoidance, or novel object recognition test, we examined the effects of rolipram, a prototypical PDE4 inhibitor, and roflumilast, a potent PDE4 inhibitor which has been approved for treatment of chronic obstructive pulmonary disease (COPD) in humans, on memory loss in APP/PS1 double transgenic mice, a widely used model for AD. In addition, we tested the effects of the PDE4 inhibitors, via ip, intra-gastric, or intra-striatum infusion, on ethanol intake and preference using the mouse two-bottle choice paradigm. Mice deficient in PDE4A, PDE4B, or PDE4D (4AKO, 4BKO, and 4DKO, respectively) and their wild type (WT) controls were tested for ethanol consumption and memory; the latter was measured in the absence or presence of beta-amyloid peptide 1-42 (Abeta42) infused into the dorsal hippocampus. Results: Similar to rolipram, roflumilast reversed memory deficits in APP/PS1 mice in all the memory tests and reduced ethanol intake and preference in C57BL/6 mice in two-bottle choice. Consistent with the results in the memory tests, roflumilast reduced the loss of neurons and neurocyte apoptosis in AD mice, as shown using HE and Nissl staining. It also reversed the decreased ratio of Bcl-2/BAX in the cerebral cortex and hippocampus of AD mice. In addition, roflumilast reversed the decreased levels of cAMP and expression of phosphorylated cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) in AD mice. Compared to the WT controls, 4AKO mice displayed significant decreases in ethanol intake and preference and reversal of Abeta42-induced memory deficits. In contrast, 4BKO mice only mimicked the ability of 4AKO mice to reduce alcohol consumption while 4DKO mice only to reverse Abeta42-induced memory deficits. In addition, levels of cAMP and phospho-CREB (pCREB) were increased in the hippocampus of 4AKO or 4DKO mice, which also showed reversal of Abeta42-induced decreases in pCREB.
Conclusions: These data suggest that PDE4 inhibitors such as roflumilast improve learning and memory in AD and reduce ethanol intake and preference likely via cAMP/CREB/BDNF signaling-mediated neuroprotection. PDE4 isoforms have different roles in mediating ethanol-drinking behavior and memory in AD. The results indicate PDE4A as a potential new target for alcohol-related dementia, although studies with animal models of alcohol-related dementia are needed to clarify this.