Short‐term environmental enrichment,in the absence of exercise,improves memory,and increases NGF concentration,early neuronal survival,and synaptogenesis in the dentate gyrus in a time‐dependent manner

Environmental manipulations can enhance neuroplasticity in the brain, with enrichment‐induced cognitive improvements being linked to increased expression of growth factors, such as neurotrophins, and enhanced hippocampal neurogenesis. There is, however, a great deal of variation in environmental enrichment protocols used in the literature, making it difficult to assess the role of particular aspects of enrichment upon memory and the underlying associated mechanisms. This study sought to evaluate the efficacy of environmental enrichment, in the absence of exercise, as a cognitive enhancer and assess the role of Nerve Growth Factor (NGF), neurogenesis and synaptogenesis in this process. We report that rats housed in an enriched environment for 3 and 6 weeks (wk) displayed improved recognition memory, while rats enriched for 6 wk also displayed improved spatial and working memory. Neurochemical analyses revealed significant increases in NGF concentration and subgranular progenitor cell survival (as measured by BrdU+ nuclei) in the dentate gyrus of rats enriched for 6 wk, suggesting that these cellular changes may mediate the enrichment‐induced memory improvements. Further analysis revealed a significant positive correlation between recognition task performance and BrdU+ nuclei. In addition, rats enriched for 6 wk showed a significant increase in expression of synaptophysin and synapsin I in the dentate gyrus, indicating that environmental enrichment can increase synaptogenesis. These data indicate a time‐dependent cognitive‐enhancing effect of environmental enrichment that is independent of physical activity. These data also support a role for increased concentration of NGF in dentate gyrus, synaptogenesis, and neurogenesis in mediating this effect. © 2013 Wiley Periodicals, Inc.     

In vivo contribution of nestin‐ and GLAST‐lineage cells to adult hippocampal neurogenesis

Radial glia‐like cells (RGCs) are the hypothesized source of adult hippocampal neurogenesis. However, the current model of hippocampal neurogenesis does not fully incorporate the in vivo heterogeneity of RGCs. In order to better understand the contribution of different RGC subtypes to adult hippocampal neurogenesis, we employed widely used transgenic lines (Nestin‐CreER^T2 and GLAST::CreER^T2 mice) to explore how RGCs contribute to neurogenesis under basal conditions and after stimulation and depletion of neural progenitor cells. We first used these inducible fate‐tracking transgenic lines to define the similarities and differences in the contribution of nestin‐ and GLAST‐lineage cells to basal long‐term hippocampal neurogenesis. We then explored the ability of nestin‐ and GLAST‐lineage RGCs to contribute to neurogenesis after experimental manipulations that either ablate neurogenesis (i.c.v. application of the anti‐mitotic AraC, cytosine‐β‐D‐arabinofuranoside) or stimulate neurogenesis (wheel running). Interestingly, in both ablation and stimulation experiments, labeled RGCs in GLAST::CreER^T2 mice appear to contribute to neurogenesis, whereas RGCs in Nestin‐CreER^T2 mice do not. Finally, using NestinGFP reporter mice, we expanded on previous research by showing that not all RGCs in the adult dentate gyrus subgranular zone express nestin, and therefore RGCs are antigenically heterogeneous. These findings are important for the field, as they allow appropriately conservative interpretation of existing and future data that emerge from these inducible transgenic lines. These findings also raise important questions about the differences between transgenic driver lines, the heterogeneity of RGCs, and the potential differences in progenitor cell behavior between transgenic lines. As these findings highlight the possible differences in the contribution of cells to long‐term neurogenesis in vivo, they indicate that the current models of hippocampal neurogenesis should be modified to include RGC lineage heterogeneity. © 2013 Wiley Periodicals, Inc.     

Age‐dependent effects of hippocampal neurogenesis suppression on spatial learning

Reducing hippocampal neurogenesis sometimes, but not always, disrupts hippocampus‐dependent learning and memory. Here, we tested whether animal age, which regulates rate of hippocampal neurogenesis, is a factor that influences whether deficits in spatial learning are observed after reduction of neurogenesis. We found that suppressing the generation of new hippocampal neurons via treatment with temozolomide, an antiproliferation agent, impaired learning the location of a hidden platform in the water maze in juvenile mice (1–2 months old) but not in adult mice (2–3 months old) or middle‐aged mice (11–12 months old). These findings suggest that during juvenility, suppression of neurogenesis may alter hippocampal development, whereas during adulthood and aging, pre‐existing neurons may compensate for the lack of new hippocampal neurons. © 2012 Wiley Periodicals, Inc.     

Right,left, and center: How does cerebral asymmetry mix with callosal connectivity?

Background: Prior research has shown that cerebral asymmetry is associated with differences in corpus callosum connectivity. Such associations were detected in histological and anatomical studies investigating callosal fiber size and density, in neuroimaging investigations based on structural and diffusion tensor imaging, as well as in neuropsychological experiments. However, little is known about typical associations between these factors, and even less about the relative influences of magnitude and direction of cerebral asymmetries. Here, we investigated relationships between callosal connectivity and cerebral asymmetry using precise measures of callosal thickness and selected cerebral structures. We considered both the direction and magnitude of the asymmetries. Methods: Associations between cerebral asymmetry and callosal thickness were investigated in 348 cognitively healthy older individuals. Results: The magnitude and direction of cerebral lateralization were significant independent predictors of callosal thickness. However, associations were small. Leftward asymmetry and increased magnitude of asymmetry were generally associated with increased callosal thickness, mostly in the callosal midbody and isthmus. Conclusions: When a large sample of normal individuals is considered, cerebral asymmetries are only subtly associated with callosal thickness. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Postnatal di-2-ethylhexyl phthalate exposure affects hippocampal dentate gyrus morphogenesis

Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate for the production of flexible polyvinyl chloride. Recent studies in humans reported a widespread DEHP exposure, raising concerns in infants whose metabolic and excretory systems are immature. DEHP is a potential endocrine-disrupting chemical, but the effects of postnatal DEHP exposure on neuronal development are unclear. The dentate gyrus (DG) is critical in the consolidation of information from short- to long-term memory, as well as spatial learning. We evaluated neurodevelopmental toxicity due to neonatal DEHP exposure by assessing neurogenesis in the DG. Newborn mice were orally administered DEHP from postnatal day (PND) 12 to 25. We performed immunostaining using neuronal markers at different stages to assess whether DEHP exposure affects neurons at specific differentiation stages at PND 26 and PND 110. We found that in mice, postnatal DEHP exposure led to a decrease in the number of Type-1, -2a, -2b, and -3 neural progenitor cells, as well as granule cells in the hippocampal DG at PND 26. Further, the results showed that neural progenitor cell proliferation and differentiation were also reduced in the hippocampal DG of the DEHP-exposed mice. However, no effect on memory and learning was observed. Overall, our results suggest that neurodevelopmental toxicity due to postnatal DEHP exposure might affect postnatal DG morphogenesis.     

间充质干细胞外泌体对海马神经元氧化应激的调控作用

目的 探讨间充质干细胞外泌体(Mesenchymal stem cell derived-exosomes,MSC-Exo)对海马神经元氧化应激的作用。方法 首先体外培养原代小鼠海马神经元,用H₂O₂刺激建立氧化应激模型,细胞计数试剂盒(Cell counting kit-8,CCK8)筛选最佳H₂O₂水平并检测不同水平MSC-Exo对细胞活力的作用,试剂盒检测超氧化物歧化酶(Superoxide dismutase,SOD)的活性,酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测DNA氧化损伤分子8-羟基脱氧鸟苷(8-hydroxy-2 deoxyguanosine,8-OHdG)的表达水平,然后免疫荧光和免疫印迹检测应激和损伤分子一氧化氮合成酶(Inducible nitric oxide synthase,iNOS)、高迁移率族蛋白B1(High mobility group box 1,HMGB1)的表达水平。结果 CCK8细胞活力实验显示,10 μg/mL及以上水平的MSC-Exo对海马神经元氧化损伤具有明显的保护作用; 与对照组比较,H₂O₂组SOD的活性显著下降,而在MSC-Exo+H₂O₂组有所提高,趋于正常; 与对照组比较,H₂O₂作用后iNOS,HMGB1,8-OHdG等分子的表达水平显著上调(P<0.01),MSC-Exo作用于模型后与H₂O₂组比较,这些分子的表达水平显著下调(P<0.01)。结论 MSC-Exo作用于H₂O₂诱导的海马神经元氧化应激模型后能够增加SOD的活性,抑制海马神经元iNOS,HMGB1,8-OHdG等分子的表达,表明MSC-Exo对海马神经元氧化应激有一定的调控作用。     

经冠状缝-额中回入路神经内镜手术治疗高血压性基底节区出血的标准化流程分析

目的 总结一种简单实施、有效的、标准的经冠状缝-额中回入路神经内镜手术治疗高血压性基底节区出血的标准化流程。方法 回顾性分析2019年4月至2021年4月按统一标准实施的经冠状缝-额中回入路神经内镜手术治疗的48例高血压性基底节区出血的临床资料。术中未使用神经导航及3D-slicer等软件辅助定位。结果 术后24 h内复查头CT显示残余血肿量中位数为2.4（1.1~3.9）ml;血肿清除率中位数为94.0%（90.0%~98.0%）。无术后再出血。出院时GCS评分中位数为13（11~14）分。术后随访6~30个月（中位数15个月）,mRS评分0~2分35例,3~4分10例,5~6分3例。结论 神经内镜下经冠状缝-额中回入路手术治疗高血压性基底节区出血是一种简单易行的手术方式,无需神经导航及3D-slicer等软件辅助定位,可以取得良好的手术效果。     

Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood via the Akt/p27 Signaling Pathway

Objective Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established.Methods SD rats were exposed to propofol on postnatal day 7(PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus(DG). The expression of pAkt and p27 were measured by western blotting. The Morris water maze, novel object recognition test,and object location test we...     

对CUS抑郁症大鼠模型海马齿状回突触改变的体视学研究

目的 运用无偏体视学方法定量研究慢性不可预知应激(chronic unpredictable stress, CUS)模型大鼠海马DG体积、DG突触密度、突触总数的改变情况.方法 筛选4～5周龄雄性SD大鼠分为对照组(n=15)和CUS组(n=23).CUS组大鼠通过孤养并结合慢性不可预知应激方式建立模型,对照组每5只为1笼,正常喂养.建模期间,每周进行糖水偏好试验.建模4周后,结合糖水偏好试验、旷场实验、高架十字迷宫实验对两组大鼠行为学表现进行评估.随后运用现代体视学与免疫组织化学相结合的方法测量两组大鼠海马DG体积、DG突触密度和突触总数.结果 经过4周CUS干预后,CUS组大鼠与对照组相比,体质量显著降低(P＜0.05),糖水偏好显著下降(P＜0.05);旷场实验中央区域路程、中央路程比和中央时间比显著降低(P＜0.05).CUS组大鼠海马DG突触密度[(0.48±0.13) /μm3]和突触总数(6.713 5×1o8)较对照组大鼠[突触密度(0.15 ±0.03)/μm3,突触总数(2.103 3×109)]显著下降(P＜0.05).结论 抑郁症模型大鼠海马DG的突触总数减少、突触密度减小,表明海马齿状回突触改变可能是抑郁症发病的重要神经结构基础之一.