游泳运动对老年大鼠学习记忆及伏隔核多巴胺含量和一氧化氮合酶表达的影响

目的:探讨游泳运动对老年大鼠学习记忆能力及伏隔核多巴胺含量和一氧化氮合酶(nNOS)表达的影响.方法:选择24月龄SD老年大鼠,随机分为2组,即老年对照组、游泳运动组,5月龄大鼠为成年对照组.对照组在笼内正常生活,不运动.游泳运动组采用递增负荷游泳运动,连续8周.8周后利用八臂迷宫测试大鼠空间学习记忆能力,高效液相色谱-电化学法检测各组大鼠伏隔核多巴胺含量,采用免疫组织化学结合图像半定量方法对伏隔核nNOS神经元的数量、面积及灰度进行测量和分析.结果:与成年对照组比较,老年对照组大鼠伏隔核多巴胺含量降低,完成八臂迷宫时间延长,工作记忆错误次数、参考记忆错误及总记忆错误次数均增加;与老年对照组比较,游泳运动组大鼠伏隔核多巴胺含量增高,完成八臂迷宫时间缩短,工作记忆错误次数、参考记忆错误次数及总记忆错误次数均减少.与成年对照组比较,老年对照组伏隔核nNOS免疫阳性细胞数量和阳性产物面积均减少,灰度差异没有统计学意义;与老年对照组比较,游泳运动组伏隔核nNOS免疫阳性细胞数量和阳性产物面积均增加,灰度差异无统计学意义.结论:长期游泳运动可提高老年大鼠的学习记忆能力,可能与长期游泳运动有效调整中枢神经递质多巴胺的合成及增强大脑伏隔核nNOS的表达有关.     

青,老年大鼠在Morris水迷宫中的学习记忆行为

本实验观察了２２￣２４月龄老年大鼠和５￣６月龄青年大鼠在Ｍｏｒｒｉｓ水迷宫中的学习记忆行为，并用定量分析方法比较两组动物在定位航行及空间搜索试验中的学习记忆，结果表明老年大鼠的寻找平台潜伏期明显延长，而其跨平台次数及在平台象限的游泳路线长度并未减少。提示２４月龄老年大鼠获取学习记忆的能力受损伤而保持记忆的能力维持正常，这可能与二种功能衰老的不同速度及不同神经基础有关。     

老年雌性和雄性大鼠学习记忆能力比较

目的观察老年雌、雄性wistar大鼠的学习记忆能力的差异,进一步探索雌激素对学习记忆的影响。方法26只18月龄健康Wistar大鼠,其中雌性16只,雄性10只,在相同环境中饲养2个月后,用Morris水迷宫测试并分析其学习记忆能力的差异。结果在各时段老年雌性大鼠的逃避潜伏期均长于老年雄性大鼠,第5～9时段雌性大鼠的逃避潜伏期显著高于雄性大鼠(P<0.01),雌性大鼠的穿台次数显著低于雄性大鼠(P<0.05)。结论雌激素撤退在老年雌性大鼠学习记忆能力下降的中起到了主要作用。     

老年大鼠在水迷宫中学习记忆能力的改变

<正>人类开始衰老即伴随着空间学习记忆能力的损害.人们巳用多样方法证实老年大鼠也有空间学习记忆能力障碍.且在人和鼠均显示明显的年龄相关的海马结构改变.本实验选用大鼠作模型研究老年性学习记忆能力改变,为研究老年性学习记忆的神经生物学提供一个较理想的模型.实验动物分青年(3月)、老年(24月)两组.检验装置是在Morris水迷宫的基础上加以改进,整个实验过程分为学习(Shaping)直线游泳(SS)、位置识别(PD)和重复获取(RA)等阶段.学习的过程是训练实验鼠在水中通过爬上平台而逃避水难.SS过程是     

老年记忆减退大鼠海马CA1区锥体细胞和神经毡线粒体的体视学研究

目的 应用电镜观察老年记忆损害大鼠海马线粒体的形态学改变.方法 青年(3月龄)和老年(26月龄)SD大鼠经Morris水迷宫测试后,以青年鼠平均逃避潜伏期正常值上限的95%和99%上限值为界将老年鼠分为老年记忆正常组和老年记忆减退组.用透射电镜观察海马CA1锥体细胞和神经毡内线粒体的体视学参数.结果 1.与青年大鼠相比,老年记忆正常大鼠海马线粒体数密度(Nv)、比膜面(Sm)、比表面(Ss)下降显著,但体密度(Vv)与青年大鼠相比无显著差异;老年记忆减退大鼠海马线粒体Nv、Ss、Sm、Vv均下降显著,且Vv、Nv的下降与老年记忆正常大鼠间有显著差异;2.老年记忆减退大鼠和老年记忆正常大鼠线粒体平均体积(V)均较青年组明显增加,但两老年组间无差异.讨论 线粒体的形态学参数体现了老年期海马线粒的代偿改变,而线粒体的功能失调可能在老年记忆损害中起重要作用.     

雌性大鼠肾上腺皮质形态及功能的增龄变化

30只Wistar雌性大鼠分为青年组(3～4月龄)、中年组(12～14月龄)及老年组(24～26月龄)。用光镜、电镜及放射免疫技术对其肾上腺皮质进行了形态及功能增龄变化的研究。见老年大鼠球状带变薄,血浆醛固酮浓度下降;束状带结构紊乱,出现出血灶,部分线粒体嵴退化、消失,滑面内质网扩张,胞浆呈现空泡,脂滴减少;网状带溶酶体及脂褐素增多,细胞间胶原纤维增多,血浆脱氢表雄酮(DHEA)浓度下降。提示老年大鼠肾上腺皮质发生了退行性变化。     

老年大鼠肾脏微分离肾小球、肾小管及动脉血管紧张素Ⅱ受体的表达

目的: 观察老年大鼠肾脏不同部位不同亚型的血管紧张素Ⅱ受体(ATR)基因表达的改变。方法: 取3月龄及24月龄雄性Wistar大鼠肾脏,行Western印迹杂交及Northern 印迹杂交检测肾皮质AT₁R的蛋白及基因表达,行冰冻切片(厚5 μm),通过激光切割、弹射微分离系统分离肾小球、肾小管及动脉,提取RNA,利用RT-PCR方法观察AT_1aR mRNA、AT_1bR mRNA及AT₂R mRNA的表达。结果: 24月龄大鼠肾脏的AT₁R在蛋白水平及基因水平均低于3月龄大鼠。应用自动激光微分离技术成功分离了大鼠肾脏的肾小球、肾小管及小动脉。24月龄大鼠肾小球AT_1aR mRNA的表达与3月龄大鼠比较无明显差异,在肾小管表达低于3月龄大鼠,动脉表达高于3月龄大鼠;AT_1bR mRNA在肾小球、肾小管表达均低于3月龄大鼠,在动脉的表达高于3月龄大鼠;AT₂R mRNA的表达在肾小管明显高于3月龄大鼠,在肾小球及动脉的表达无明显差异。结论: 老年大鼠的肾小球、肾小管及肾内动脉各型血管紧张素受体的改变不同,有可能在肾脏增龄性改变中起重要作用。     

孕烯醇酮对大鼠空间学习记忆能力和ChAT蛋白表达的影响

目的:研究孕烯醇酮(Pregnenolone,PREG)干预对老年雄性SD大鼠空间学习记忆能力的影响,探讨PREG的潜在神经保护作用及其机制。方法:24月龄雄性SD大鼠40只,随机分为对照组(A组)、溶剂对照组(B组)、低剂量PREG(0.5 mg/kg)干预组(C组)、高剂量PREG(2.0 mg/kg)干预组(D组),隔日腹腔注射一个月,利用Y迷宫训练评估PREG对实验大鼠空间学习记忆能力的影响,运用免疫荧光技术和Western Blot检测分析大鼠记忆相关脑区ChAT蛋白表达的变化。结果:Y迷宫训练结果显示D组大鼠平均连续正确反应次数为7.5±1.35,明显多于其他各组;免疫荧光检测结果显示D组大鼠前额叶、颞叶、海马内ChAT免疫阳性的细胞数量相应是26.8±2.6、19.8±2.6、25.8±2.4,明显多于其他处理组;Western Blot检测显示D组大鼠前额叶、颞叶、海马皮层组织ChAT蛋白的表达明显高于其他各组(P0.05)。结论:PREG有助于改善老年雄性SD大鼠空间学习记忆能力,其作用机制可能是促进了大鼠记忆相关脑区ChAT的表达上调,提高了胆碱能神经元细胞的功能活性。     

催产素在大细胞基底核中对大鼠学习记忆的影响

目的：探讨催产素在大细胞基底核（NBM）内对大鼠学习记忆的影响。方法：于Wistar雄性大鼠大细胞基底核内微量注入不同剂量（0,0.2,2,8nmol）的催产素及催产素拮抗剂-阿托西班（Atosiban）,然后用水迷宫检测大鼠的学习记忆能力及其量效关系。结果：NBM内注入2及8nmol催产素组的大鼠找到平台的时间（潜伏期）显著延长,0.2nmol组与对照组比较未见有显著性差异,先注入催产素拮抗剂后再注入催产素,其找到平台的时间与正常组之间没有显著性差异。结论：NBM内的催产素损害了大鼠的学习记忆能力,其作用是通过催产素受体介导的。     

海马及第三脑室内移植颈上神经节组织对老年大鼠学习记忆的改…

以回避反应为指标，检测了１９只２４月龄老年Ｗｉｓｔａｒ大鼠的学习记忆能力。于老年大鼠双侧海马或第三脑室移植新生大鼠颈上神经节后２周，观察到学习记忆能力显著改善，海马内移植后以避暗反应检查，进洞潜伏自１７．５±１５．５ｓ延至３７６．７±２７０．８ｓ（ｐ＜０．０１）。同期非移植或假移植术大鼠的学习记忆能力仍处于较低水平。第三脑室内移植后以跳台法检测，大鼠为回避电击在平台停留５ｍｉｎ所需电击时间为１１．     

Naltrexone reverses age-induced cognitive deficits in rats

We evaluated young (3-4 months) and aged (22-24 months) male Sprague-Dawley rats in an attentional set-shifting procedure that assessed reversal, intradimensional shift (IDS), and extradimensional shift (EDS) discrimination learning tasks within one test session. These aspects of discrimination learning are sensitive to damage to distinct regions of frontal cortex. Compared to young animals, aged rats were significantly impaired on the EDS task and did not demonstrate significant impairment on the reversal or IDS tasks. The opioid antagonist naltrexone (2mg/kg, ip) was administered to young and aged rats prior to testing to assess possible improvements in aged-related cognitive impairments. Naltrexone (2mg/kg) attenuated the impairments in cognitive function in the EDS task for aged animals, but did not alter any task performance in the younger group. These results suggest that normal aging in rats is associated with impaired medial frontal cortex function as assessed by this attentional set-shifting procedure and opioid mediated mechanisms may represent a therapeutic target for drugs to improve cognitive deficits associated with aging.     

Pattern separation deficits may contribute to age-associated recognition impairments

Normal aging is associated with impairments in stimulus recognition. In the current investigation, object recognition was tested in adult and aged rats with the standard spontaneous object recognition (SOR) task or two variants of this task. On the standard SOR task, adult rats showed an exploratory preference for the novel object over delays up to 24 h, whereas the aged rats only showed significant novelty discrimination at the 2-min delay. This age difference appeared to be because of the old rats behaving as if the novel object was familiar. To test this hypothesis directly, rats participated in a variant of the SOR task that allowed the exploration times between the object familiarization and the test phases to be compared, and this experiment confirmed that aged rats falsely "recognize" the novel object. A final control examined whether or not aged rats exhibited reduced motivation to explore objects. In this experiment, when the environmental context changed between familiarization and test, young and old rats failed to show an exploratory preference because both age groups spent more time exploring the familiar object. Together these findings support the view that age-related impairments in object recognition arise from old animals behaving as if novel objects are familiar, which is reminiscent of behavioral impairments in young rats with perirhinal cortical lesions. The current experiments thus suggest that alterations in the perirhinal cortex may be responsible for reducing aged animals' ability to distinguish new stimuli from ones that have been encountered previously.     

"I've seen it all before": explaining age-related impairments in object recognition. Theoretical comment on Burke et al. (2010)

Animal models are useful in elucidating the neural basis of age-related impairments in cognition. Burke, Wallace, Nematollahi, Uprety, and Barnes (2010) tested young and aged rats in several different protocols to measure object recognition memory and found that object recognition deficits in aged rats were consistent with these rats behaving as if novel objects were familiar, rather than familiar objects being treated as novel (that is, forgotten). A similar pattern of behavior has been observed in young rats with perirhinal cortex lesions. Moreover, age-related impairments in object recognition were uncorrelated with deficits in spatial learning in the water maze, a task that requires the integrity of the hippocampus and is also reliably impaired in aged rats. Taken together, these findings support functional specialization of structures within the medial temporal lobe "memory system," as well as the independence of age-related deficits in different cognitive domains. They also potentially form a foundation for neurobiological study of age-related impairments in perirhinal cortex function.     

Glucose and age-related changes in memory

Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to - or may exacerbate - the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.     

Proactive interference effects on short-term memory in rats: II. Effects in young and aged rats

Whether the short-term memory impairments of aged rats in an operant delayed-matching task is attributable to increased susceptibility to proactive interference (PI) was tested. Groups of young and aged rats were trained on the task, and the previously reported delay-dependent deficit of aged rats was replicated. The aged rats showed a significantly greater decline in performance on previous-response-opposite trials compared with previous-response-same trials than did young rats, when tested over the same range of delay intervals, suggesting a higher sensitivity to PI. However, this effect was established against a higher overall baseline performance of the young animals on both types of trial. When the young and aged animals were equated for performance on previous-response-same trials (by increasing the range of delay intervals used for testing the young animals), the interaction effect was abolished. Thus, the delay-dependent deficits of aged rats are independent of their sensitivity to PI.     

An evaluation of spatial information processing in aged rats

The spatial learning abilities of young, middle-age, and senescent rats were investigated in two experiments using several versions of the Morris water maze task. In Experiment 1, Long-Evans hooded rats were trained to find a submerged escape platform hidden within the water maze. During this phase of testing, aged rats exhibited acquisition deficits compared with either young or middle-age subjects. With continued training, however, all age groups eventually achieved comparable asymptotic levels of performance. Subsequent testing in Experiment 1 revealed that following original training, aged rats were not impaired in learning a novel escape location or in their ability to locate a visible, cued escape platform. In an attempt to identify the basis of the age-related impairments observed in Experiment 1, naive young and aged rats in Experiment 2 were initially tested for their ability to locate a cued escape platform in the water maze. During this phase of testing, the escape latencies of both young and aged rats rapidly decreased to equivalent asymptotic levels. Subsequent analyses revealed that following cue training, young subjects exhibit a significant spatial bias for the region of the testing apparatus where the platform was positioned during training. In contrast, aged rats showed no spatial bias. Training was continued in Experiment 2 using a novel submerged platform location for each subject. During these place training trials, the escape latencies of senescent rats were longer than those of young subjects. These impairments were also accompanied by a lack of spatial bias among aged rats relative to young control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electric activity in the neocortex of freely moving young and aged rats

Electroencephalographic activity of the neocortex was evaluated in young (5-7 months) and aged (26-28 months) rats. All animals in the aged group showed behavioral impairment in a spatial task (water maze). A neocortical electroencephalogram was derived simultaneously from 16 different neocortical locations and was subjected to spectral analysis. The frequency of occurrence and duration of high-voltage spindles was determined in two sessions, each involving a total of 30 min alert immobility. Changes in spectral characteristics and high-voltage spindles in response to scopolamine administration were also evaluated. The power of high-frequency activity (8-20 Hz) was significantly reduced in the aged subjects. This was greatest in the temporo-occipital regions, while no significant changes were seen in the mediofrontal region. Scopolamine resulted in a large power increase in all frequency bands, but the increase in the higher-frequency range (8-20 Hz) was significantly less in the aged group. The incidence of high-voltage spindles was 6 times higher and their total duration was 9 times longer in aged rats, with virtually no overlap with the young group. In young rats, scopolamine increased the incidence and total duration of high-voltage spindles, while it decreased both parameters in the aged subjects. Cholinergic neurons in the nucleus basalis appeared shrunken in the aged animals. These findings demonstrate that reliable electroencephalographic changes are present in the neocortex of the aged rat, and that some of the physiological alterations may be due to the pathological changes in the cholinergic nucleus basalis.     

老年大鼠空间记忆减退与cNOS基因表达变化

目的：从基因表达角度研究原生型NOS（cNOS,包括神经元型nNOS和内应型eNOS）与老年记忆减退发生的关系。方法：用Morris水迷宫将老年大鼠筛选为记忆正常和记忆减退两组,以老年记忆减退大鼠作为老年记忆减退模型;用半定量反转录一聚合酶链反应（RT－PCR）方法测定nNOS和eNOS的mRNA含量。结果：（1）海马组织中老年记忆正常组和老年记忆减退组较青年组nNOS和eNOSmRNA含量均下降,nNOS以记忆减退组下降更为显著;（2）小脑组织中老年记忆减退组nNOS和eNOSmRNA含量的下降与老年记忆正常组和青年组均有显著差异。（3）额叶组织nNOSmRNA含量三组之间均无显著差异;eNOSmRNA含量老年记忆正常组和老年记忆减退组技青年组均下降,以记忆减退组下降更为显著。结论：老年记忆减退的发生可能与有关脑区cNOS基因表达下降有关。     

Age-related impairment in complex maze learning in rats: relationship to neophobia and cholinergic antagonism

Scopolamine was utilized to assess cholinergic muscarinic blockade on the performance of young (3 months) and aged (23 months) male F-344 rats in a 14-unit T-maze task. Prior to training, a portion of each age group received a gustatory neophobia test (percent consumption of a novel sucrose solution) to assess involvement of norepinephrine systems implicated in age-related impairments of rats in other memory tasks. All rats were pretrained in one-way active avoidance (1.0 mA) on 3 consecutive days. Rats meeting criterion (8/10 avoidances on last day) began maze training the next day consisting of 10 trials on 2 consecutive days. The task required the rat to negotiate each of 5 maze segments within 10 sec to avoid scrambled footshock (1.0 mA). Rats received an intraperitoneal injection of either scopolamine hydrochloride (0.5 mg/kg or 0.75 mg/kg) or saline vehicle 30 min prior to maze testing. Consistent with past reports, aged rats were more neophobic (i.e., consumed less sucrose) than were young rats, but the degree of neophobia was not significantly correlated with maze error performance in either age group. Also consistent with previous studies, aged rats were significantly impaired, compared to young counterparts, in all maze performance measures including errors, alternation errors, runtime, and shock frequency and duration. Significant scopolamine-induced deficits were observed in both age groups, but only in errors and alternation strategy. No age by drug interaction was manifested in any performance measure indicating that scopolamine impaired learning of young and aged rats equivalently.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spatial learning and motor deficits in aged rats

Young (3 months) and aged (24 months) rats were compared on a range of behavioural tests. The aged animal were impaired in their acquisition of a spatial learining task in the Morris water maze, as well as showing deficits in motor coordination, swimming efficiency, and spontaneous locomotion and exploration in an open field. Qualitative observation and correlation analyses indicated that the aged group was heterogeneous in the degree of impairments manifested by the individual animals, and suggested that the development of impairments may progress with aging at different rates in the various tasks and possibly in different underlying neuroanatomical systems.