Demyelination Induces the Decline of the Myelinated Fiber Length in Aged Rat White Matter

To determine the exact reason for the age‐related decline of the myelinated fiber length in white matter, we performed this study. In middle‐aged rats, there was age‐related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle‐aged rat white matter might make the age‐related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable. However, in old‐aged female rats, the unmyelinated fibers with large and small diameters significantly degenerated together and that the unmyelinated fibers formed from the demyelination of the myelinated fibers could not replenish the age‐related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the significant decline of the myelinated fiber length in aged white matter. Anat Rec, 292:528–535, 2009. © 2009 Wiley‐Liss, Inc.     

Enriched Environment Increases the Myelinated Nerve Fibers of Aged Rat Corpus Callosum

In this study, the effect of enriched environment (EE) on the spatial learning of aged rats was examined, and then the effects of EE on the aged corpus callosum (CC) were investigated by means of the modern stereological methods. We found that EE significantly improved the spatial learning of aged rats. The CC volume, the total volume of the myelinated fibers and total volume of the myelin sheaths in the CC, the total length of the myelinated fibers in the CC of enriched rats were significantly increased when compared to standard rats. The increase of the myelinated fibers in enriched rat CC might provide one of the structural bases for the enrichment‐related improvement of the spatial learning. This study provided, to the best of our knowledge, the first evidence of environmental enrichment‐induced increases of the CC and the myelinated fibers in the CC of aged rats. Anat Rec, , 2012. © 2012 Wiley Periodicals Inc.     

P> 短期丰富生存环境增加中老年雄性大鼠海马结构内有髓神经纤维的总长度/P>

目的 探讨短期丰富生存环境干预对正常中老年雄性大鼠海马结构及海马内有髓神经纤维的影响。 方法 将20只14月龄的雄性SD大鼠随机分为丰富生存环境组与空白对照组,前者在丰富生存环境条件下饲养4个月,后者在普通环境中饲养4个月后,采用Morris水迷宫测试两组大鼠的空间学习能力;运用透射电子显微镜和体视学方法对两组大鼠海马结构及海马内有髓神经纤维进行定量研究。 结果 丰富生存环境组大鼠空间学习能力与空白对照组之间不存在显著性差异;丰富生存环境组与空白对照组相比较,海马结构总体积两组间无显著性差异。丰富生存环境组海马结构内有髓神经纤维的总体积、有髓神经纤维总长度、有髓神经纤维平均直径显著增加。 结论 短期丰富生存环境干预对14月龄雄性大鼠海马有髓神经纤维具有显著性影响。这一研究结果为将来寻找延缓大脑衰老进程的行为学手段提供了重要的理论依据。     

短期丰富生存环境增加中老年雄性大鼠海马结构内有髓神经纤维的总长度

目的探讨短期丰富生存环境干预对正常中老年雄性大鼠海马结构及海马内有髓神经纤维的影响。方法将20只14月龄的雄性SD大鼠随机分为丰富生存环境组与空白对照组,前者在丰富生存环境条件下饲养4个月,后者在普通环境中饲养4个月后,采用Morris水迷宫测试两组大鼠的空间学习能力;运用透射电子显微镜和体视学方法对两组大鼠海马结构及海马内有髓神经纤维进行定量研究。结果丰富生存环境组大鼠空间学习能力与空白对照组之间不存在显著性差异;丰富生存环境组与空白对照组相比较,海马结构总体积两组间无显著性差异。丰富生存环境组海马结构内有髓神经纤维的总体积、有髓神经纤维总长度、有髓神经纤维平均直径显著增加。结论短期丰富生存环境干预对14月龄雄性大鼠海马有髓神经纤维具有显著性影响。这一研究结果为将来寻找延缓大脑衰老进程的行为学手段提供了重要的理论依据。     

No loss of synaptic proteins in the hippocampus of aged, behaviorally impaired rats

The levels of three different synaptic proteins in the hippocampus of young (6 months of age) and aged (26-27 months of age) Long Evans rats were examined using quantitative Western blotting. An important feature to this study is that prior to the neurobiological analysis, hippocampal function was determined by assessing spatial learning ability in the Morris water maze. A subset of the aged rats was impaired on the learning task while the remaining aged cohort performed within the range of young rats. The amount of immunoreactivity for synaptophysin, synaptotagmin, and synaptosomal associated protein-25 did not differ between the young and aged rats. In addition, the aged rats with severe cognitive impairment had levels of these synaptic proteins that were similar to those of the aged rats with preserved cognitive function. This finding of no change in the levels of synaptic proteins suggests that substantial synapse loss in the hippocampal formation does not underlie cognitive decline in normal aging.     

大鼠大脑白质及白质内有髓神经纤维的性别与年龄差异

目的:研究正常年轻和中老年组雌雄性大鼠大脑白质及白质内有髓神经纤维之间的性别差异,并探讨大脑发育过程中性别差异随年龄增加的改变。方法:运用透射电子显微镜和体视学方法对6~8月龄的年轻Long-Evans大鼠及18月龄同种中老年大鼠大脑白质及其有髓神经纤维进行定量研究。结果:年轻组雄性大鼠大脑白质、有髓神经纤维及其髓鞘的总体积均显著大于雌性,而中老年组雌性大鼠大脑白质、有髓神经纤维体积密度、有髓神经纤维及其髓鞘的总体积均显著大于雄性。结论:年轻组及中老年组大鼠大脑白质、白质内有髓神经纤维及其髓鞘总体积均存在性别差异,随着年龄的增长,雄性大鼠大脑白质及白质内有髓神经纤维体积的减少较雌性更为明显。     

大鼠海马结构内有髓神经纤维老年性改变的体视学研究

目的 探讨雌性Long-Evans大鼠海马结构及其内有髓神经纤维的老年性改变。 方法 运用透射电子显微镜和体视学方法分别对5只青年(6月龄)、5只中老年(18月龄)和6只老年(28月龄)雌性Long-Evans大鼠海马结构及其内有髓神经纤维进行定量研究。 结果 青年组、中老年组和老年组大鼠的海马结构总体积,海马结构内有髓神经纤维的体积分数和总体积,有髓神经纤维的长度密度和有髓神经纤维平均直径均未见显著性改变。中老年组大鼠海马结构内有髓神经纤维总长度与青年组相比增加了63.6%,老年组有髓神经纤维总长度与中老年组相比下降了47.5%,老年组有髓神经纤维总长度与青年组比较下降了13.8%。 结论 本研究结果进一步支持正常老年大脑的有髓神经纤维存在广泛性老年改变。     

跑步训练对中老年大鼠海马结构及其内有髓神经纤维的影响

目的探讨跑步训练对中老年雌性大鼠海马结构及海马结构内有髓神经纤维的影响。方法将10只14月龄的雌性SD大鼠随机分为跑步训练组和空白对照组,分别进行4个月的跑台训练和普通标准环境饲养。4个月后采用Morris水迷宫对两组大鼠的空间学习能力进行测试,然后运用透射电子显微镜和新的体视学方法对大鼠大脑海马结构及其内有髓神经纤维进行定量研究。结果与对照组相比,训练组老年雌性大鼠空间学习能力明显增强;海马结构总体积、海马结构内有髓神经纤维总长度显著增加,但海马结构内有髓神经纤维的总体积未见明显改变。海马结构内有髓神经纤维总长度分布图表明,训练组有髓神经纤维总长度的增加主要是由于细小直径的有髓神经纤维长度增加所致。结论跑步训练对中老年雌性大鼠的空间学习能力、海马结构及其内有髓神经纤维有明显的影响。     

Teaching old rats new tricks: age-related impairments in olfactory reversal learning

Recent work suggests that normal aging may be associated with decline in different brain systems. In the present study, young and aged Long-Evans rats were tested in a spatial version of the Morris water maze dependent on medial temporal lobe function and also on an odor discrimination reversal task previously used to investigate orbitofrontal function. Aged rats acquired the odor discrimination problems normally but were impaired in acquiring subsequent reversals of the problems. A subset of the aged rats also exhibited impaired spatial learning in the water maze. There was no correlation between reversal performance and spatial learning in the aged rats, indicating that the reversal learning impairment was not related to decline in medial temporal lobe function. Instead the performance of the aged rats on the odor discrimination task resembled that of young rats with neurotoxic lesions of orbitofrontal cortex. These data indicate that rats show independent decline of different brain systems during normal aging and suggest orbitofrontal cortex as one prefrontal area where changes may be localized for further study.     

Muscarinic receptor-mediated GTP-Eu binding in the hippocampus and prefrontal cortex is correlated with spatial memory impairment in aged rats

The present study examined muscarinic receptor/G-protein coupling in the hippocampus and the prefrontal cortex of young and aged Long-Evans rats characterized for spatial learning ability in the Morris water maze. In a highly sensitive time-resolved fluorometry GTP-Eu binding assay, muscarinic-mediated GTP-Eu binding was severely blunted in hippocampus (-32%) and prefrontal cortex (-34%) as a consequence of aging. Furthermore, the magnitude of decreased muscarinic-mediated GTP-Eu binding was significantly correlated with the severity of spatial learning impairment in hippocampus and prefrontal cortex of aged rats and was specifically decreased in the subset of aged rats that were spatial learning impaired when compared to the aged unimpaired and the young rats. Western blot data indicated a preservation of the membrane-bound M1 receptor and the Galphaq/11 protein in both brain regions. These data demonstrate that muscarinic signaling is severely impaired as a consequence of normal aging in a manner that is closely associated with age-related cognitive decline.     

短期丰富生存环境对老年雄性大鼠大脑白质及白质内有髓神经纤维的影响

目的 探讨短期丰富生存环境干预对老年雄性大鼠大脑白质及白质内有髓神经纤维的影响.方法 将20只24月龄雄性SD大鼠分别在丰富生存环境条件和普通标准环境下饲养4个月后,从每组随机抽取4只大鼠,用透射电子显微镜和体视学方法比较两组大鼠大脑白质及白质内有髓神经纤维的改变. 结果 丰富生存环境组大鼠的白质总体积,白质内有髓神经纤维总长度和总体积,有髓神经纤维轴突总体积分别较标准对照组显著增大,但有髓神经纤维平均内径、外径、髓鞘总体积、髓鞘平均厚度、髓鞘平均内、外周长、有髓神经纤维断面面积、髓鞘断面面积及轴突断面面积较对照组均无明显差异. 结论 短期丰富生存环境干预对24月龄雄性大鼠的大脑白质和白质内有髓神经纤维均有明显的影响.提示短期丰富生存环境可能促使老年雄性大鼠白质内已经发生脱髓鞘改变的有髓神经纤维出现髓鞘再生.     

短期丰富生存环境对中老年雌性大鼠海马结构及其内有髓神经纤维的影响

目的 探讨短期丰富生存环境干预对中老年雌性大鼠海马结构及其内有髓神经纤维的影响。 方法 将20只14月龄的雌性SD大鼠随机分为丰富生存环境组和标准环境组,每组各10只,对丰富生存环境组的动物给予4个月丰富生存环境干预, 标准环境组于普通标准环境下饲养4个月;然后每组各随机选取5只,采用Morris水迷宫对大鼠的空间学习能力进行测试,然后运用透射电子显微镜和体视学方法分别对大鼠大脑海马结构及其内有髓神经纤维进行定量研究。 结果 短期丰富生存环境组中老年雌性大鼠与标准环境组相比,其空间学习能力明显增强;丰富生存环境组海马结构内有髓神经纤维总长度和总体积分别显著增加了43.4%和47.4%,且有髓神经纤维总长度的增加主要是由于细小直径的有髓神经纤维长度增加所致。海马结构总体积和海马结构内有髓神经纤维直径未见改变。 结论 4个月丰富生存环境干预对于14月龄雌性大鼠空间学习能力、海马内有髓神经纤维均有显著性影响。     

CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging

Normal cognitive aging is associated with deficits in memory processes dependent on the hippocampus, along with large-scale changes in the hippocampal expression of many genes. Histone acetylation can broadly influence gene expression and has been recently linked to learning and memory. We hypothesized that CREB-binding protein (CBP), a key histone acetyltransferase, may contribute to memory decline in normal aging. Here, we quantified CBP protein levels in the hippocampus of young, aged unimpaired, and aged impaired rats, classified on the basis of spatial memory capacity documented in the Morris water maze. First, CBP-immunofluorescence was quantified across the principal cell layers of the hippocampus using both low and high resolution laser scanning imaging approaches. Second, digital images of CBP immunostaining were analyzed by a multipurpose classifier algorithm with validated sensitivity across many types of input materials. Finally, CBP protein levels in the principal subfields of the hippocampus were quantified by quantitative Western blotting. CBP levels were equivalent as a function of age and cognitive status in all analyses. The sensitivity of the techniques used was substantial, sufficient to reveal differences across the principal cell fields of the hippocampus, and to correctly classify images from young and aged animals independent of CBP immunoreactivity. The results are discussed in the context of recent evidence suggesting that CBP decreases may be most relevant in conditions of aging that, unlike normal cognitive aging, involve significant neuron loss.     

大鼠大脑皮质有髓神经纤维老年性改变的定量研究

目的:探讨中枢神经系统是否普遍存在老年性轴突变性和髓鞘破坏。方法:运用透射电子显微镜和体视学方法分别对青年组(6～8月龄)和老年组(18月龄以上)Long-Evans大鼠大脑皮质及皮质内有髓神经纤维进行定量研究。结果:老年大鼠的皮质体积,皮质内有髓神经纤维的总长度和总体积以及直径较年青大鼠有所下降,但这些降低均无统计学意义。结论:老年大鼠大脑皮质不存在显著性有髓神经纤维退行性改变。     

大鼠大脑白质及白质内有髓神经纤维老年性改变的体视学研究

目的 探讨老年大鼠大脑白质及白质内有髓神经纤维的改变.方法 运用透射电子显微镜和体视学方法分别对年轻组和老年组Long-Evans大鼠大脑白质及其内有髓神经纤维进行定量研究.结果 老年组大鼠大脑白质总体积,有髓神经纤维总长度分别下降了24.1%和41%;老年组大鼠有髓神经纤维体积密度、髓鞘体积密度和纤维直径分别增加了30%、23.9%和31%,具有统计学意义.但是有髓神经纤维长度密度、有髓神经纤维总体积和髓鞘的总体积没有显著老年性改变.结论 正常老年大脑的萎缩主要是由白质体积的下降引起的.正常老年大脑白质的有髓神经纤维总长度显著性降低,并且主要是由于白质内细小直径的有髓神经纤维丢失所造成的.     

雄性大鼠大脑半球白质及其内有髓神经纤维老年改变的侧别差异

目的 探讨雄性大鼠左右大脑半球白质及其内有髓神经纤维是否存在显著性差异,以及每侧大脑半球白质及其内有髓神经纤维的老年性改变是否一致.方法运用透射电子显微镜和体视学方法分别对5只年轻(6～8月龄)和4只老年(18月龄)雄性Long-Evans大鼠左侧、右侧大脑半球白质体积及白质内有髓神经纤维体积、长度和直径进行定量研究.结果年轻组大鼠和老年组大鼠左右大脑半球白质体积及白质内有髓神经纤维体积、长度和直径均不存在显著性差异.每侧大脑半球白质及其内有髓神经纤维总长度和总体积均随年龄增加而降低,右侧半球白质体积、右侧半球白质内有髓神经纤维总体积和左侧半球白质内有髓神经纤维总长度随年龄增长分别显著性降低32.9%、28.6%和49.3%.结论正常年轻和老年雄性Tong-Evans大鼠两侧大脑半球的白质及其内有髓神经纤维均不存在显著性侧别差异.老年雄性Long-Evans大鼠右侧大脑半球白质体积、右侧大脑半球白质内有髓神经纤维的总体积和左侧大脑半球白质内有髓神经纤维总长度存在显著老年性改变.     

大鼠坐骨神经超微结构的老年性变化

为了研究老年大鼠坐骨神经超微结构特点,随机取3月龄(成年组)和24月(老年组)龄正常SD大鼠各10只,用电镜观察两组间坐骨神经超微结构的差异。结果显示:老年组大鼠坐骨神经内有髓纤维的百分比、轴突间胶原纤维密度以及Schwann细胞胞质中脂褐质沉积密度均多于成年组(P<0.05);但无髓纤维之百分比少于成年组(P<0.05)。上述结果提示坐骨神经内的有髓纤维与无髓纤维百分比、轴突间胶原纤维密度以及Schwann细胞胞质中脂褐质沉积密度是衡量大鼠坐骨神经老化的形态标志之一。     

Latent learning of spatial information is impaired in middle‐aged rats

The present study determined if the middle age related impairment that occurs with nonspatial latent learning also occurs in spatial latent learning. Thirty young (3‐months‐old) and 30 middle‐aged (12‐months‐old) male Sprague–Dawley rats were given either pre‐exposure to spatial cues surrounding a Barnes maze (SpatialPX), or pre‐exposure to just the maze (MazePX). They were then given 10 training trials in which they had to find a hidden escape box while experiencing an aversive environment produced by bright lights and wind. Results showed that young rats given the SpatialPX condition demonstrated faster escape latencies and fewer errors than young rats given the MazePX condition. However, middle‐aged rats given the SpatialPX condition did not show this improved performance. These findings indicate that the middle age learning deficit is not task specific, but rather is a general impairment in latent learning, possibly due to the early degeneration of the entorhinal cortex. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 309–315, 2013     

Aging affects transcranial magnetic modulation of hippocampal evoked potentials

Transcranial magnetic stimulation (TMS) is being proposed as a method of choice for the treatment of clinical depression, yet its action in the brain is still not well understood. In previous studies we found that TMS has a long-term effect on reactivity of the hippocampus to perforant path stimulation. Since the efficacy of antidepressants is highly age-dependent, we studied possible age-related effects of TMS on hippocampal evoked responses. Young adult (3 months), aging (10 months) and aged (24-26 months) awake rats were subjected to daily TMS for one week, followed by measurements of several parameters of reactivity to perforant path stimulation in the anesthetized rat. TMS did not affect responses of the hippocampus to single perforant path stimulation, but reduced drastically paired-pulse and frequency dependent depression in the young and aging but not the old rats. Likewise, TMS increased LTP expression in the young but not the old rats, and reduced the efficacy of serotonin modulation of reactivity of the hippocampus, in the young but not the old rats. Thus, long term effects of chronic TMS on local GABAergic inhibition are highly age dependent.     

Effect of age and cognitive status on basal level AP-1 activity in rat hippocampus.

Activator protein-1 (AP-1) was examined at multiple levels (mRNA, DNA binding, composition) in hippocampus of young and aged rats that were behaviorally characterized for spatial memory. GFAP mRNA was measured as a gene product known to increase with aging and to be regulated by AP-1. The activity of Jun-amino terminal-kinase (JNK) was also assessed. Levels of c-jun and c-fos mRNAs were unchanged with aging or spatial learning ability. Abundance of GFAP mRNA was significantly increased in aged hippocampus but did not correlate with spatial learning. Total AP-1 binding activity was unaltered with age or cognitive ability. In hippocampus of young, aged unimpaired and aged impaired rats, AP-1 consists mainly of c-Jun, phosphorylated c-Jun (p-c-Jun), JunD, and smaller amounts of c-Fos. JNK is constitutively active in young and aged hippocampus. We conclude that the basal expression of c-fos and c-jun mRNA, overall AP-1 binding activity and AP-1 composition are not influenced by aging or cognitive ability.