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1.
快速老化痴呆模型小鼠SAMP8学习记忆能力的增龄性变化   总被引:11,自引:2,他引:9  
目的对快速老化痴呆模型小鼠SAMP8学习记忆能力的增龄性变化进行较系统的研究,为利用该模型进行其他研究提供实验依据。方法此实验选用1、4、8、12月龄的快速老化痴呆模型小鼠SAMP8,与同龄的正常老化小鼠SAMR1作对照,从老化度评分、避暗实验、Morris水迷宫实验和自主活动实验等方面观察了SAMP8小鼠学习记忆能力的增龄性变化。结果与对照组SAMR1相比,SAMP8小鼠随月龄增加老化度评分呈增高趋势,在8、12月龄的老化度评分值显著高于同龄对照组(P<0.05);避暗实验中,8、12月龄的SAMP8小鼠在电击24h后进入暗箱的潜伏期比同龄SAMR1小鼠显著缩短(P<0.05);Morris水迷宫实验中,1、4月龄SAMP8小鼠找到暗台的潜伏时间与同龄SAMR1小鼠相比差异无显著性,而8、12月龄SAMP8小鼠与同龄对照组相比,潜伏时间显著延长(P<0.05);从自主活动实验看,1、4、8月龄SAMP8小鼠单位时间内自主活动次数与同龄SAMR1小鼠相比无显著变化,而12月龄SAMP8小鼠与同龄对照组相比单位时间内自主活动次数显著减少(P<0.05)。结论SAMP8小鼠随月龄增长学习记忆能力逐渐减退;与同龄对照组相比,8、12月龄SAMP8小鼠出现明显衰老特征,表现出学习记忆能力明显低下,故可作为老化痴呆的动物模型用于痴呆有关研究。  相似文献   

2.
目的观察8-氧鸟嘌呤脱氧核苷(8-oxo-7,8-dihydroguanine,8-oxo-dG)在快速老化小鼠SAMP8海马不同区域的表达,探讨其变化与SAMP8增龄的关系。方法选用1、4、8、12月龄快速老化小鼠SAMP8(每组各6只),对照组为同龄抗快速老化小鼠SAMR1(每组各6只),用免疫组化法检测海马不同区域内8-oxo—dG的表达水平。结果8-oxo-dG在海马不同区域均有表达,且主要在海马神经细胞胞核内表达。对照组SAMR1小鼠海马各区域8-oxo-dG的吸光度定量结果显示各月龄组间无统计学差异(P〉0.05);1、4月龄组SAMP8小鼠海马各区域8-oxo-dG的吸光度定量结果与同龄匹配的SAMR1小鼠间无统计学差异(P〉0.05);8、12月龄组SAMP8小鼠海马各区域8-oxo-dG的吸光度定量结果分别显著高于1月龄和4月龄组(P〈0.05),也分别显著高于同龄SAMP1对照组(P〈0.05)。结论8-oxo-dG在SAMP8快速老化小鼠海马中的水平随增龄而显著增高。  相似文献   

3.
目的研究孔圣枕中丹对SAMP8海马CA1区形态结构、PAS染色阳性颗粒状结构(PGS)及星形胶质细胞纤维酸性蛋白(GFAP)的影响,探讨其改善SAMP8小鼠学习记忆的作用机制。方法选用7个月龄雄性的SAMP8小鼠分为模型组、治疗组;同时选用同源同月龄雄性的SAMR1小鼠作为正常老化对照组。检测指标:苏木精-伊红染色观察小鼠海马CA1区形态结构;免疫组化分析小鼠海马CA1区GFAP的表达;PAS病理特殊染色观察小鼠海马CA1区糖原的表达。结果孔圣枕中丹组海马CA1区神经元病理改变较模型组有明显改善;孔圣枕中丹PGS颗粒数有不同程度的减少,PGS颗粒体积减少,低密度颗粒数增加,与模型组比较差异有统计学意义(P<0.05);孔圣枕中丹组GFAP面密度与模型组、比较差异有统计学意义(P<0.01)。结论孔圣枕中丹能通过对海马神经元组织结构的保护作用来提高SAMP8小鼠的认知功能。  相似文献   

4.
目的 研究快速老化模型小鼠(senescence accelerated mice,SAM)学习记忆能力及其大脑皮层、海马和下丘脑单胺递质含量的增龄性变化及它们之间的关系。方法 分别采用跳台实验和穿梭箱实验测定SAM的被动和主动回避反应能力,采用高效液相色谱电化学检测法测定脑内单胺递质的含量。结果 2月龄快速老化亚系SAM-prone/8(SAMP8)的被动和主动回避反应能力已较同龄抗快速老化亚系SAM-resistance/1(SAMR1)明显降低,且其主动回避反应能力随增龄进一步降低。同时,SAMP8大脑皮层、海马及下丘脑内单胺递质水平多明显高于同龄SAMR1,且随增龄明显增高。结论 SAMP8学习记忆能力的衰退可能与其相关脑区单胺递质的变化密切相关。  相似文献   

5.
目的观察FKBPs(FK506 blinding proteins)配体噻嗪酰胺衍生物(HD5-6)对SAMP8快速老化小鼠学习记忆能力和海马神经元的影响,以及对SAMP8小鼠海马神经元基因表达谱的影响。方法选用10月龄快速老化的SAMP8小鼠20只,随机分为痴呆组、HD5-6组;另选10月龄正常老化的SAMR1小鼠10只作为正常对照组。各组分别腹腔注射药物35 d,并于29 d采用Morris水迷宫实验评价各组小鼠学习记忆能力的变化。HE染色观察海马区神经元形态;TUNEL观察海马神经元凋亡情况,用基因芯片技术检测HD5-6组和痴呆组小鼠海马神经元基因表达谱的变化差异。结果与正常对照组相比,痴呆组在定位航行实验中表现出明显的学习记忆障碍,逃避潜伏期显著延长(P0.05),HD5-6组自3 d开始逃避潜伏期比痴呆组明显缩短(P0.05);空间探索实验中HD5-6组跨平台次数、原平台象限停留时间明显多于痴呆组(P0.05)。与正常对照组相比,痴呆组海马区神经元数量明显减少,细胞排列紊乱,大量的神经元细胞核固缩,深染、坏死,其神经元凋亡指数(51.73±4.48)%明显高于正常对照组(28.02±11.25)%(P0.05),HD5-6干预的SAMP8小鼠海马区神经元病理改变明显改善,海马神经元凋亡指数(20.47±2.25)%明显降低(P0.01)。HD5-6组与痴呆组海马神经元基因表达谱相比,表达差异在2倍以上的基因有118条,表达上调的为9条,表达下调的为109条。其中有功能的mRNA中,表达上调的有4条,表达下调的有21条。结论 HD5-6能够改善快速老化小鼠SAMP8的学习记忆能力和海马神经元病理改变,并可能通过对基因表达谱产生影响而发挥明显的抗衰老作用。  相似文献   

6.
目的:观察快速老化小鼠(Senescence-accelerated mouse,SAM)海马神经元的基本离子通道特点,并对抗快速老化亚系(SAM-resistance/1,SAMR1)与快速老化亚系(SAM-prone/8,SAMP8)的基本离子通道特点进行了比较,探讨离子通道变化在衰老中的可能角色.方法:应用全细胞记录方式,观察并比较原代培养SAMR1和SAMP8海马神经元的电压门控离子通道及膜参数.结果:原代培养SAMR1和SAMP8海马神经元电压门控Na+通道电流(INa)和电压门控延迟整流K+通道电流(Ik)的电学特点和幅度基本一致.SAMP8的电压门控Ca2+通道电流(ICa)和瞬时外向K+通道电流(IA)的幅值则大于相同培养天数的SAMR1.经膜电容校正所得的ICa电流密度也表现出增大的变化规律.结论:SAMP8与SAMR1神经元间IA和ICa的差异可能与其神经系统变异而产生的学习记忆功能下降有关.  相似文献   

7.
目的观察自主跑笼运动对快速老化P8小鼠精神行为学及血清促肾上腺皮质激素(ACTH和皮质醇(Cor)水平的影响。方法雄性3月龄快速老化P8小鼠20只,随机数字表法分为运动组和非运动组,每组10只;抗快速老化R1小鼠5只为对照组。所有小鼠均给予同样标准环境饲养,运动组施加自主跑笼运动训练(每周5天)。2月后采用自主活动仪和高架十字迷宫行为学测试评估小鼠精神行为学变化,同时放射免疫方法检测小鼠血清ACTH及Cor水平。结果快速老化P8小鼠非运动组与同月龄抗快速老化R1小鼠对照组比较,自主活动次数(104.4±33.3,150.0±39.9)和高架十字迷宫开放臂停留时间(157.1±44.9,202.8±39.2)均显著减少(P0.05)。快速老化P8小鼠自主活动次数运动组(159.6±66.6)与非运动组(104.4±33.3)比较显著增加(P0.05);高架十字迷宫测试开放臂停留时间运动组(173.6±51.4)与非运动组(157.1±44.9)比较,差异无统计学意义(P0.05)。快速老化P8小鼠非运动组与抗快速老化R1小鼠对照组比较,血清ACTH(28.49±8.24,47.86±9.52)及Cor水平(3.19±0.88,5.01±0.79)均显著减少(P0.05)。快速老化P8小鼠运动组(50.35±6.64,5.23±1.42)较非运动组(28.49±8.24,3.19±0.88)均显著增高(P0.05)。结论 5月龄快速老化P8小鼠有明显精神行为异常,自主跑笼运动对快速老化P8小鼠精神行为异常有一定改善,可能是通过上调下丘脑-垂体-肾上腺轴活性而实现的。  相似文献   

8.
快速老化小鼠海马神经元电压门控离子通道特点   总被引:5,自引:0,他引:5  
目的:观察快速老化小鼠(Senescence-accelerated mouse,SAM)海马神经元的基本离子通道特点,并对抗快速老化亚系(SAM-resistance/1,SAMR1)与快速老化亚系(SAM-prone/8,SMAP8)的基本离子通道特点进行了比较,探讨了离子通道变化在衰老中的可能角度,方法:应用全细胞记录方式,观察并比较原代培养SAMR1和SAMP8海马神经元的电压门控离子通道及膜参数。结果:原代培养SAMR1和SAMP8海马神经元电压门控Na^2 通道电流(INa)和电压门控延迟整流K^ 通道电流(IK)的电学特点和幅度基本一致。SAMP8的电压门控Ca^2 通道电流(ICa)和瞬时外向K^ 通道电流(IA)的幅值则大于相同培养天数的SAMR1。经膜电容校正所得的ICa电流密度也表现出增大的变化规律。结论:SAMP8与SAMR1神经元间IA和ICa的差异可能与其神经系统变异而产生的学习记忆功能下降有关。  相似文献   

9.
目的 探讨脑血流量、血脑屏障(BBB)通透性、脑葡萄糖跨膜转运蛋白表达情况随年龄增大对阿尔茨海默病(AD)模型小鼠SAMP8认知能力的影响. 方法 选择SAMP8小鼠及正常同源抗快速老化小鼠R1(SAMR1)各10只进行观察.采用Morris水迷宫测定小鼠的学习记忆能力,激光多普勒仪测定脑血流量,荧光分光光度计法测定BBB通透性,Western blotting测定葡萄糖转运蛋白(GLUT)1和3的表达. 结果 与SAMR1相比,SAMP8的认知能力早在4月龄时即已出现明显损伤,表现为思维僵化、学习过程减慢.随着年龄增大,SAMP8脑血流明显下降,BBB渗漏更为严重,皮层和海马的GLUT1和GLUT3表达也有不同程度地改变.脑血流、BBB完整性、GLUT1和GLUT3表达受年龄和品系影响明显,并与认知能力高度相关. 结论 衰老及缺血引起的血管损伤、能量供给不足是造成AD神经元功能异常及导致认知障碍的主要原因.  相似文献   

10.
电针对SAMP8小鼠海马NCAM和NF-κB表达的影响   总被引:1,自引:0,他引:1  
目的 研究电针对阿尔茨海默病(AD)模型小鼠海马神经细胞黏附分子(NCAM)和核转录因子κB(NF-κB)的影响,从神经细胞黏附角度探讨电针治疗AD的作用机制.方法 快速老化模型小鼠(SAMP8)24只采用随机数字表法分为模型组、模型+针刺组(简称模针组),每组12只;抗快速老化模型小鼠(SAMR1)12只为空白组,每日一次电针模针组小鼠"百会"、"涌泉"穴,连续治疗21 d.应用免疫组织化学染色、原位杂交方法 检测各组小鼠海马组织NCAM、NF-κB蛋白及mRNA的表达.结果 与模型组比较,模针组小鼠NCAM(0.231±0.007)、NF-κB蛋白(0.367±0.012)及mRNA(0.528±0.016,0.308±0.001)阳性表达明显增强,差异有统计学意义(P<0.05).结论 电针可通过提高NF-κB的表达,诱导NCAM的合成,促进神经细胞黏附.  相似文献   

11.
The senescence-accelerated mouse strain P6 (SAMP6) is an inbred mouse that represents a clinically relevant model of senile osteoporosis. However, whether osteoporotic SAMP6 mice have cognitive deficits remains largely unexplored. Here, we used Morris water maze to assess reference memory and working memory performance in SAMP6 mice and SAMR1 controls, at 4 and 8 months of age. In addition, unbiased stereological techniques were used to estimate total neuron number in hippocampal CA1 subfield of the mice used in the behavioral study. Morris water maze test revealed impairments in working memory but not in reference memory of the 4- and 8-month-old SAMP6 mice compared with the SAMR1 mice at the same age. However, there were no significant differences in the total numbers of neurons in hippocampal CA1 subfield when comparing 4-month-old SAMR1 and 4-month-old SAMP6 and 8-month-old SAMR1 and 8-month-old SAMP6, which indicate that, in SAMP6 mice, the structural correlates of working memory deficits are to be found in parameters other than the number of neurons in hippocampal CA1 subfield. These findings suggest that SAMP6 mice exhibit selective cognitive deficits and highlight the importance of this mouse model for studying the brain alterations associated with osteoporosis.  相似文献   

12.
Shi F  Gan W  Nie B  Takagi Y  Hayakawa H  Sekiguchi M  Cai JP 《Neuroreport》2012,23(8):508-512
Our previous studies have shown that substantial amounts of 8-oxoguanine are present in the DNA and RNA in the hippocampi of old senescence-accelerated mice (SAMP8); however, oxidative damage to DNA and RNA in the other regions of the brain from a month after birth to the onset of aging has not been examined completely. In this study, we analyzed the amount of 8-oxoguanine in DNA and RNA in the temporal and frontal lobes of SAMP8 during aging by the immunohistochemical method. Compared with age-matched control acceleration-resistant mice (SAMR1), 8- and 12-month-old SAMP8 had increased amounts of 8-oxoguanine in the DNA and RNA in the frontal lobe, whereas in the temporal lobe, this trend began to appear as early as 4 months. The levels of 8-oxoguanine in the temporal lobe were significantly higher than those in the frontal lobe. These results indicate that nucleic acid oxidative damage occurs as an age-associated phenomenon, and can occur more easily in the temporal lobe than in the frontal lobe of SAMP8.  相似文献   

13.
This study examined age-dependent deficits in the learning and memory of inferential tasks, using an established senescence-accelerated mouse model in age-related brain dysfunction (SAMP8) and its genetically related inbred strain (SAMR1). The mice learned two sets of nonspatial odor-odor pairs by association learning successively (i.e., A-->B, X-->Y, then B-->C, Y-->Z). They were tested in transitive inference (i.e., A-->C, X-->Z) and symmetrical inference (i.e., C-->B, Z-->Y). In the probe test of A-->C, X-->Z transitive inference, 1-month-old SAMP8 and control SAMR1 at the same age significantly chose the alternative based on transitive inference, but 4- and 7-month-old SAMP8 performed at a random chance level, in comparison with unambiguous inference by control SAMR1 at the same ages. During the test of C-->B, Z-->Y symmetrical inference, SAMP8 at 1 month of age made errors as frequently as control SAMR1 at the same age, but SAMP8 at 4 and 7 months of age made more errors than SAMR1 at the same ages. At 4 and 7 months of age, SAMP8 made more errors than 1-month-old SAMP8. Control SAMR1 did not show such an age-related deficient. These results indicate that SAMP8 mice have age-related learning and memory deficits in the ability to perform inferential tasks. Age-related hippocampal dysfunction is suggested to be the cause of these age-related deficits in old SAMP8 mice during the performance of inferential tasks mediated by declarative memory.  相似文献   

14.
Senescence of the cerebrovascular system and an abnormal function of the blood–brain barrier have been related with Alzheimer's disease. We studied here the time-course of blood–brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice, which is a murine model of senescence and is also considered a model of Alzheimer's disease. We used a previously described method that allows evaluating blood–brain barrier integrity by observing Evans blue extravasation from brain blood vessels. Three brain regions (cortex, hippocampus and hippocampal fissure) of SAMP8 brains were analyzed at 3, 6, 9, 12 and 15 months of age. Moreover, genetically related senescence-accelerated mouse resistant 1 (SAMR1) and ICR-CD1 mice were studied. Results indicate that Evans blue permeability in SAMP8 and SAMR1 increases from 6 to 15 months in the three studied regions. At 15 months of age, SAMP8 and SAMR1 mice showed higher Evans blue extravasation in CA1 and Fissure than ICR-CD1 mice. Further studies are required to understand the senescence process in SAMR1 mice, as blood–brain barrier alterations in old age have unexpectedly been observed. On the other hand, as blood–brain barrier permeability in SAMP8 mice increases with age, blood–brain barrier alterations may contribute to the cerebral pathology observed in this strain.  相似文献   

15.
Ye X  Meeker HC  Kozlowski P  Carp RI 《Brain research》2004,995(2):158-166
Scrapie is a fatal, but slow, infectious disease. C57BL/6J, SAMP8 (a strain that develops early senescence), SAMR1 (a strain that is resistant to senescence) and AKR/J (a progenitor of the SAM strains) mice were infected with 22A, 139A, 22L and ME7 scrapie strains. Histopathological stains included haematoxylin and eosin (HE), and periodic acid-Schiff (PAS). Vacuolation was found in the brains of all scrapie-infected mice. The 22A strain caused more extensive vacuolation in the brains of SAMP8 and SAMR1 mice than in C57BL mice. PAS-positive plaques (PP) were found in 22A-infected mice in cortex, corpus callosum, hippocampus, subependymal zone area and thalamus. PP were significantly increased in 22A-infected SAMR1 mice compared to mice from other scrapie-infected strains. Clusters of small, round, homogeneous PAS-positive granular structures (PGS) were found in all mouse strains, especially in aging control and 22A-infected C57BL mice, predominantly in the stratum radiatum of the CA1, CA2 and CA3 areas of the hippocampus. Some of these structures were also observed in stratum oriens and piriform cortex, and in cerebellar Purkinje cell areas. Some of the PGS were associated with astrocytes and blood vessels. Each granule was 1-5 microm in diameter and there were clusters consisting of several to 40 PGS; the sizes of the clusters ranged from 10 to 80 microm in diameter. There were more PGS clusters in uninfected C57BL and AKR mice than in uninfected SAMP8 and SAMR1 mice. PGS were not increased in scrapie-infected mice. These findings suggest that PGS accumulation was more dependent on the genetic information of the mouse strain, whereas PP and vacuolation patterns depended on the scrapie strain-mouse strain combination.  相似文献   

16.
In order to discover and identify the key protein biomarkers in the aging process, we performed a differential proteomic analysis of hippocampus and cortex in 5- and 15-month old senescence-accelerated mouse prone 8 (SAMP8) as well as in control strain SAM/resistant 1 (SAMR1). Using 2-DE combined with MALDI TOF/TOF mass spectrometry, about 1700 protein spots were isolated, and three groups of differentially expressed proteins were identified. The first group contained the strain-specific and non-age-related differential proteins that were differentially expressed in SAMP8 compared with SAMR1 mice. The changes might be implicated in the genetic difference between SAMP8 and SAMR1 mice; specifically, the proteins ubiquitin carboxyl-terminal esterase L3, mitofilin, adenylate kinase 4, and an unnamed protein product (gi|12847201). The proteins in the second group were age-specific, which were differentially expressed between 5- and 15-month old SAM mice. Those proteins are particularly interesting since the changes were aging-related and some of them were previously reported to be expressed in Alzheimer's disease patients. These proteins included N-myc downstream regulated gene 2, enolase 2, Cu/Zn superoxide dismutase, myosin, and two unnamed protein products (gi|74214304 and gi|74178239). The protein in the third group was SAMP8 specific-age-related protein, which was identified as heme binding protein 1. The present study provides new information about SAMP8 specific and aging-related protein changes in brain. Further investigations will be performed to reveal the significance of these proteins in brain aging process and the potential roles as biomarkers for effective diagnosis and therapy.  相似文献   

17.
We analyzed effects of aging on behavioral rhythms in the mouse showing senescence acceleration, SAMP8 strains. The free-running rhythms had longer free-running periods (τ) in SAMP8 than in the control strain (SAMR1). Drinking of melatonin promoted the adaptation to advanced LD in SAMR1 but not in SAMP8, although both strains exhibited melatonin MT1 and MT2 receptors. The present results suggest that melatonin promotes the adaptation to advanced LD cycles in normal aging mice.  相似文献   

18.
We compared the expression patterns of neurotrophin genes in the brain of senescence-accelerated mouse (SAMP8) which shows age-related impairment of learning behavior, with SAMR1 control which shows normal aging. By Northern blot analysis, NT-3 mRNA levels in the cortex were higher in SAMP8 than in SAMR1 mice during development, whereas in the midbrain, hippocampus and forebrain, NT-3 expression levels in SAMP8 were lower than those in SAMR1. At early stages, although NGF mRNA levels in SAMP8 were lower than those in SAMR1, BDNF mRNA levels were almost equivalent in both strains. By in situ hybridization analysis, NT-3 mRNA signals in the CA1 and CA2 regions in SAMP8 were shown to be reduced at early stages. However, BDNF mRNA signals were almost equivalent in both SAMR1 and SAMP8.  相似文献   

19.
Many studies have explored the premature aging of accelerated senescence-prone (SAMP8) mice. However, the cause of premature aging in this strain remains unknown. We analyzed the expression of ecotropic, xenotropic, and polytropic murine leukemia viruses (MuLVs) in the brains of accelerated senescence-resistant (SAMR1) and SAMP8 mice. No ecotropic mRNA was detected in SAMR1 mice, and only Akv-type ecotropic MuLV mRNA was detected in SAMP8 mice. Restriction mapping of the full-length infectious E-MuLV genome from SAMP8 confirmed its identity as Akv. mRNAs corresponding to a prototypical polytropic MuLV and to an unusual xenotropic MuLV were detected at equal levels in SAMP8 and SAMR1 mice, but no infectious virus of either host range type was detected. In order to determine the cellular localization of Akv expression in SAMP8 mice, we used immunohistochemistry and electron microscopy to detect expression of the E-MuLV capsid gag (CAgag) gene in striatum, brainstem, hippocampus, and cerebellum of 12-month-old SAMR1 and SAMP8 mice. The CAgag antigen was seen in the neurons, oligodendroglia, and vascular endothelium of these brain regions of SAMP8 mice, but not in SAMR1 mice. To evaluate the correlation between activation of astrocytes and expression of Akv, we performed double-immunohistochemical staining for both glial fibrillary acidic protein (GFAP) and CAgag in SAMR1 and SAMP8 mice. Strong astrocytic activation and extensive vacuolation were observed around CAgag-positive neurons in SAMP8 mice, whereas in SAMR1 mice neither astrocytosis nor vacuolation were present. CAgag antigen was also localized in astrocytes of the hippocampus region of SAMP8 mice. Electron micrography showed that a number of vacuoles were found in the cytoplasm of MuLV-positive neurons and the extracellular space surrounding these neurons showed lytic changes. These results suggest that endogenous Akv provirus is expressed in neurons, astrocytes, vascular endothelium, and oligodendroglia in the brains of SAMP8 and that this virus could play an important role in the brain aging processes in this mouse strain.  相似文献   

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