Age-Induced White Matter Changes in the Human Brain: A Stereological Investigation

In the present pilot study, age-related white matter changes were investigated by the use of design-based stereological methods. In the brains of elderly subjects, the total volume of the white matter and the total volume of the myelinated fibers therein were lower than in those of young subjects (15% and 17%, respectively), but the differences were not statistically significant. The total length of the myelinated fibers of the white matter in the elderly group of 86,000 km was, statistically, significantly decreased by 27% compared with 118,000 km in the young group. This loss of the total nerve fiber length was accompanied in particular by a decline of the myelinated fibers with a small diameter. The mean diameter of the myelinated fibers in the young group was significantly smaller than in the old group, but the relative size distributions of the myelinated fiber diameters between the young and old groups were similar. Our findings show that the atrophy of the human white matter during ageing is probably caused by a loss of myelinated fibers with a small diameter.     

大脑白质有髓神经纤维髓鞘超微结构定量研究的体视学方法

目的:运用新的体视学方法研究大鼠白质有髓神经纤维髓鞘超微结构,以期为以后各种有关髓鞘超微结构的相关研究提供可靠的方法学依据.方法:6～8月龄雌性Long-Evans大鼠.运用电镜技术及相应的体视学方法计算白质内有髓神经纤维的总长度、有髓神经纤维髓鞘总体积、有髓神经纤维及轴突直径、髓鞘断面面积、髓鞘内外周长、髓鞘平均厚度.结果:获得了正常6～8月龄雌性Long-Evans大鼠有髓神经纤维总长度及髓鞘超微结构的各项数据,两种不同方法得到的髓鞘平均厚度并没有显著性差异.结论:把新的体视学方法和电子显微镜结合起来定量研究了大鼠大脑白质有髓神经纤维髓鞘超微结构,所描述的方法为以后进行髓鞘超微结构的定量研究提供了有用的工具.     

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.     

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.     

Side differences of the age-related changes in the white matter and the myelinated nerve fibers in the white matter of female rats

The present study tested if there were side differences of the white matter and the myelinated fibers in the white matter of female rats, and if there were side differences in the age-related changes of the white matter and the myelinated fibers in the white matter of female rats. Five young, five middle-aged and five aged female Long-Evans rats were quantitatively investigated using electron microscopic technique and stereological methods. We found no side differences of the white matter volume, the total volume, total length and mean diameter of the myelinated fibers in the white matter of young, middle-aged, and aged female rats. When compared to middle-aged female rats, the total length of the myelinated fibers in the white matter of the left hemisphere in aged female rats was decreased significantly, but the total length of the myelinated fibers in the white matter of the right hemisphere in aged female rats was non-significantly decreased. Our data indicated that there were no significant side differences in the white matter and the myelinated fibers in the white matter in young, middle-aged, and aged female rats. However, we demonstrated that the aged-related changes of the myelinated fibers in the white matter of the left hemisphere and right hemisphere were different. The results obtained in the present study will provide biological basis for the understanding of the asymmetry of cerebral functions.     

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.     

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。     

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。     

Stereological Methods for Estimating the Myelin Sheaths of the Myelinated Fibers in White Matter

In the present study, efficient and unbiased stereological techniques to investigate the myelin sheaths of the myelinated fibers in rat white matter were established. In the present design, four tissue blocks were obtained from the entire white matter of rat brain in a uniform, random fashion. Isotropic, uniform random (IUR) sections were ensured by the use of the isector technique. One section with the thickness of 60 nm was cut from the center of each epon block. Eight to 10 fields of vision were randomly photographed under a transmission electron microscope. The total length of the myelinated fibers and the total volume of the myelin sheaths in the white matter were the products of the length density, volume density, and the volume of the white matter obtained with the Cavalieri principle. The mean areas of the myelinated fibers profiles and myelin sheaths were estimated with the point counting technique. The inner and outer perimeters of the myelin sheaths were estimated by the use of a line grid, and the thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. The described methods will provide very useful tools for future quantitative studies of changes in the myelin sheaths of white matter in various experimental conditions and in various neurodegenerative diseases. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

大鼠大脑白质无髓神经纤维老年改变的机制探讨

目的 运用体视学方法研究大鼠大脑白质无髓神经纤维的老年性改变,探讨导致老年白质有髓神经纤维总长度降低的确切原因,并探讨性别因素在老年大脑改变中所起的作用.方法 6～8月龄Long-Evans大鼠9只和18月龄同种大鼠8只.用电镜技术及相应的体视学方法计算白质内无髓神经纤维的体积密度、长度密度和白质内无髓神经纤维的总体积和总长度.结果 雄性和雌性大鼠大脑白质无髓神经纤维总长度均无显著的老年性降低.白质内无髓神经纤维总体积在雌性组存在显著的老年性降低,从年轻组的平均32.79mm3下降到了老年组的平均18.60mm3.雄性大鼠无髓神经纤维总体积老年性降低虽无显著性,但也从年轻组的平均34.79mm3下降到老年组的平均24.02mm3.降低高达31%.年轻组与老年组的各项指标中雄性与雌性动物间均不存在显著的性差别. 结论老年大鼠大脑白质存在大直径无髓神经纤维的显著件丢失,同时存在的细小直径的有髓神经纤维脱髓鞘改变,在一定程度上掩盖了老年白质内小直径无髓神经纤维的丢失.     

Unbiased stereological quantification of unmyelinated fibers in the rat brain white matter

We applied unbiased stereological principles to estimate the volume of white matter and the total volume and length of the unmyelinated fibers in the white matter of the rat brain. The mean volume of the rat brain white matter was 119 mm³. The mean total length and the mean total volume of the unmyelinated fibers in the white matter were 323 km and 35 mm³, respectively. The described method provides a useful tool for future quantitative studies of changes in the unmyelinated fibers of white matter in various experimental conditions and in various neurodegenerative diseases.     

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.     

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。     

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。     

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。     

Stereological Investigation of the Age‐Related Changes of the Myelinated Fibers in the Hippocampus of Male Rats

The decline of hippocampus‐dependent learning and memory during normal aging is not associated with neuron death and synapse loss. Until now, age‐related changes in the myelinated fibers of the hippocampus have not been investigated. Therefore, in this study, the myelinated fibers in the hippocampi of young (6 months), middle‐aged (18 months), and old‐aged (28 months) male Sprague‐Dawley rats were studied with transmission electron microscope and stereological methods, following spatial learning tests in a Morris water maze. The results showed that hippocampus‐dependent spatial learning was impaired in old‐aged rats but that the total volume, length, and mean diameter of the myelinated fibers in the hippocampus, as well as the hippocampal volume, remained constant during the normal aging process. Our results suggest that the age‐related decline in hippocampus‐dependent spatial learning is not attributable to myelinated fiber changes in the hippocampus and that other, undetermined factors are responsible. Anat Rec, 297:1490–1497, 2014. © 2014 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。     

White matter loss in healthy ageing: a postmortem analysis

Age-related brain changes are widely documented. Because of differences in measurement methods and case selection, the reported effects of age on regional grey and white matter brain volumes, however, are much more pronounced and widespread in neuroimaging than in postmortem studies. Consequently, the magnitude of the effect that is specific to chronological age remains unresolved. We present postmortem volume measurements for 26 cortical, subcortical and white matter regions, in 24 human brains aged 46-92 years, free of neuropathological abnormalities. Significant age-related loss was observed in anterior and posterior white matter but not in total grey matter volumes. Further analyses on five cortical subregions previously reported to exhibit large age-related loss on MRI yielded negative results. These analyses demonstrate smaller changes with age than those reported in imaging studies. Although this discrepancy between postmortem and imaging studies may partly be explained by the increase in noise of the neuroimaging data with age, our results suggest that healthy brain ageing is a process affecting predominantly white matter not grey matter.