Neuropathology of ALS: Spheroids

I briefly review spheroids observed in the anterior horns of the spinal cord in amyotrophic lateral sclerosis (ALS). Spheroids are argentophilic bodies more than 20 μm in diameter. Recently, some connections between the proximal axonal swellings including spheroids and the perikarya have been reported in some ALS patients with a short clinical course or mild depletion of anterior horn neurons. Most of the cell bodies directly connected with the axonal swellings appear normal, and spheroids are considered to be one of the hallmarks of the early histological changes in this disorder. Spheroids are strongly positive with anti-phosphorylated neurofilament antibody, and are also positive with calcitonin gene-related peptide and anti-peripherin antibody. Some spheroids are immunostained with anti-synaptophysin antibody and anti-ubiquitin antibody. Spheroids are not immunostained with anti-phosphorylated tau antibody, or high molecular weight microtubule associated proteins. Electron microscopically, spheroids are usually composed of densely packed accumulation of 10 nm neurofilaments with a variety of orientations, plus vesicles, dense bodies and mitochondria. When the swellings of the initial segment is relatively pronounced, the undercoating is obscured and the neurofilaments become interwoven in some parts. In the first internode of the myelinated axons, as the swellings become larger, the neurofilaments lose their parallel orientation and become intermingled. Large accumulation of neurofilaments resembling spheroids in the perikarya of large anterior horn cells suggests that spheroids could be derived not only from the axon including the proximal portion, but also from the perikarya. Structures apparently identical to axonal spheroids are observed at the light and electron microscopic levels in the proximal portion of axons of anterior horn cells in animal models intoxicated with β, β'-iminodipropionitrile (IDPN), or with aluminum, in hereditary canine spinal muscular atrophy (HCSMA). The pathogenetic mechanism is probably associated with an impairment in slow axonal transport which particularly affects the neurofilaments in IDPN and aluminum intoxication. Impairment of slow axonal transport of neurofilaments also plays an important role in the pathogenesis of ALS. The average diameter of even normalappearing initial segment is larger in ALS than in the controls. The perikarya connected with the swollen proximal axons and their dendrites almost always appear normal. These findings suggest that the slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in ALS as well as animal models for human ALS. However, techniques to analyze slow axonal transport in humans still remain tobe developed. Recently, overexpression of neurofilament subunits in transgenic mice produces a condition resembling ALS. The transgenic model may offer an interesting perspective not only for testing therapeutic strategies but also for investigating in a systematic way the various genetic and environment factors controlling the onset and progression of the disease and might yield new insights on the etiology of ALS.     

Blood velocity assessment using 3D bright-blood time-resolved magnetic resonance angiography.

Blood velocity is a functional parameter that is not easily assessed noninvasively, especially in small animals. A new noninvasive method that uses magnetic resonance angiography (MRA) to measure blood flows is proposed. This method is based on the time-of-flight (TOF) phenomenon. By initially suppressing the signal from the stationary spins in the area of interest, it is possible to sequentially visualize only the signal from the moving spins entering a given volume. With this method, 3D cine images of the blood flow can be generated by positive contrast, with unparalleled spatial (<200 microm) and temporal resolutions (<10 ms/image). As a result, it is possible to measure flow in sinuous paths. The present method was applied in vivo to measure the blood velocity in mouse carotid arteries. Because of its robustness and simplicity of implementation, this method has numerous potential applications for fundamental studies in small animal models.     

MR显微成像检测活体阿尔茨海默病转基因小鼠老年斑沉积的效果

目的利用MR显微成像技术研究阿尔茨海默病转基因小鼠老年斑的沉积情况。方法2只17个月龄阿尔茨海默病转基因[V717I]小鼠和2只野生型小鼠，行活体T2WI，然后对照影像定位结果进行组织学切片及免疫组织化学染色。观察T2WI中老年斑的沉积情况以及其与免疫组织化学染色结果的对应关系。结果转基因小鼠T2WI上显示大脑皮层和海马区可见点状低信号，且部分低信号可以和组织学切片所显示的老年斑相对应；野生型小鼠T2WI未见明显的低信号，免疫组织化学染色也未见到染色阳性的斑块。结论MR显微成像技术检测老年斑的沉积是可行的，且可用来特异性地诊断阿尔茨海默病。     

克氏螫虾与中国对虾微量元素与氨基酸含量的比较

对克氏螯虾和中国对虾的不同部位所含游离氨基酸和重要微量元素进行了比较。结果表明,克氏螯虾某些部位中游离氨基酸和微量元素的含量高于中国对虾。提示克氏螯虾可能具有与中国对虾相似的药用价值。     

化学品环境管理与水生实验动物

从分析化学品的特性入手，在概述化学品的环境管理对水生实验生物需求和国内外水生实验生物发展现状的基础上，从加强化学品环境管理的科学基础建设出发，对我国水生实验生物的研究与发展的标准化、产业化、必要的资质认可及信息交流提出建议。     

斯氏狸殖吸虫感染多种动物及体内发育的研究

目的 :以不同数量斯氏狸殖吸虫囊蚴 ,分别感染大白鼠 ,小白鼠和豚鼠 ,定期解剖观察虫体。方法 :经1 5、30、45、60、75、90、1 1 0和 1 2 5d分别解剖观察虫体在实验动物体内发育 ,分布及虫体检出率。结果 :大鼠在感染 90d后虫体可以逐步发育成熟并产卵 ,而小白鼠和豚鼠体内只能查到童虫阶段。结论 :初步证实大白鼠是斯氏狸殖吸虫的适宜宿主 ,小白鼠和豚鼠体内的虫体全部处于滞育阶段 ,不能发育为成虫     

基底动脉缝隙连接蛋白的分布

目的：探讨正常脑血管缝隙连接蛋白的分布。方法：采用RT—PCR、免疫组化方法测定多种缝隙连接蛋白在大白兔基底动脉的表达。结果：(1)RT—PCR发现大白兔基底动脉血管组织中至少存在Xx45、Cx43、Cx40和Cx37四种缝隙连接蛋白mRNA表达；(2)免疫组化证实Cx45和Cx43主要分布于血管内皮，平滑肌细胞间末见Cx45和Cx43的染色。结论：大白兔基底动脉血管组织存在丰富的缝隙连接蛋白的表达，与体内其它弹力血管相比，缝隙连接蛋白的分布模式有其特殊性。     

A perspective on measurement of mutations in vivo.

The development of transgenic mouse lines with target genes that are suitable for tissue-specific mutagenesis studies is an important contribution to the field of environmental mutagenesis. These models can accommodate many of the questions relating to metabolism, distribution and relative potency of mutagens as well as providing a more comprehensive system for the identification of mutagens. However, the lesions that the field has learned about methods, development and validation from the use of in vitro systems must be applied to the development and validation of transgenic models.     

敌枯双慢性毒性实验的病理形态学研究——实验大鼠脏器组织病理变化

将150只SD大鼠随机地分成Ⅰ,Ⅱ,Ⅲ,Ⅳ四个实验组和一个对照组(Ⅴ)。实验组敌枯双剂量分别为1.0,0.2,0.05及0.01mg/kg,均用去离子水配成相应浓度的染毒水,由动物自由摄取,对照组摄入去离子水。于实验第29.5,55周分两批处死。经组织病理学检查,结果发现:敌枯双可引起甲状腺滤泡上皮细胞萎缩甚至脱屑,其发生率(Ⅲ组为63.64%)与对照组(0%)比较差异有高度显著性(P<0.01);睾丸曲细精管各级生精细胞减少、萎缩甚至完全消失,其发生率(Ⅳ组为58.33%)与对照组(8.33%)比较差异有显著性(P<0.01);对心肌、肝组织也有不同程度的损伤.