Effects of AETT-Induced Neuronal Ceroid Lipofuscinosis on Learning Ability in Rats

Abstract: The behavioral effects of ceroid-lipofuscin accumulation, induced by intraperitoneal administration of acetyl-ethyl-tetramethyl-tetralin (AETT) in Wistar rats for 3 months, were examined in the present studies. A significant increase in neuronal ceroid-lipofuscin was demonstrated neuropathologically as well as morphometrically. Although the AETT-intoxicated rats showed neither alteration of locomotor activity nor shock sensitivity, a significant impairment of learning ability, especially an acquisition trial in passive avoidance tests, was observed. Results of the present studies indicate the possibility that a diffuse lipofuscin accumulation causes a learning impairment in rats. The results also imply the possibility of a significant role of age-related lipofuscin accumulation in the dementing processes of human especially in the elderly.     

重庆市正常青少年牙列指数测量分析

目的建立重庆市正常牙合青少年牙颌模型牙列指数的正常值,为正畸临床提供依据.方法选取重庆市正常牙合青少年牙颌模型92付(男45付,女47付),测量牙冠宽度、牙弓宽度,计算Bolton指数和Pont指数,对测量结果进行统计分析并与国内外相关资料进行对比研究,对Bolton指数和Pont指数的临床应用价值进行评价.结果Bolton指数和Pont指数存在种族和地区差异,结论Bolton指数和Pont指数在正畸临床中均有一定的应用价值,临床上应参照本民族和地区的标准.     

Acrometageria: A spectrum of “premature aging” syndromes

A child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers-Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson-Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley-Liss, Inc.     

突触功能必需基因参与线虫衰老的调控(英文)

目的鉴定参与线虫衰老的神经内分泌调控的新基因。方法鉴于神经系统在衰老调控中的重要作用,通过寿命分析和脂褐质自发荧光的检测,从编码突触蛋白的遗传位点中筛选参与衰老调控的基因。我们还进一步检查了这些遗传位点相应的突变体的永久性幼虫形成情况,探讨它们是否可能受胰岛素样信号通路的调控。结果遗传位点 unc-10,syd-2,hlb-1,dlk-1,mkk-4,scd-2,snb-1,ric-4,nrx-1,unc-13,sbt-1,unc-64 可能参与线虫衰老的调控。而且在衰老的调控中,unc-10,syd-2,hlb-1,dlk-1,mkk-4,scd-2,snb-1,ric-4,nrx-1 的功能可能与unc-13,sbt-1,unc-64相反。肠道脂褐质自发荧光的检测进一步证明了筛选出的各基因对应突变体的长寿或短寿表型,是由减慢或缩短的组织衰老所致。在筛选出的基因中,syd-2,hlb-1,mkk-4,scd-2,snb-1,ric-4,unc-64 也参与了永久性幼虫形成的调控。另外,daf-2突变增强了syd-2和hlb-1的表达,降低了mkk-4,nrx-1,ric-4,sbt-1,rpm-1,unc-10,dlk-1,unc-13 的表达。daf-16突变提高了syd-2和 hlb-1 的表达,降低了mkk-4,nrx-1,sbt-1,rpm-1,unc-10,dlk-1,unc-13 的表达. 结论突触功能可能在个体寿命和永久性幼虫形成的调控机制中具有重要的作用。     

Maturation and aging of the axonal cytoskeleton: biochemical analysis of transported tubulin.

Changes in solubility and axonal transport of tubulin during maturation and aging have been investigated using sciatic motor fibers of rats at 4, 7, 14, 30, and 80 weeks of age. One to six weeks after injection of L-[35S]methionine into the spinal cord, labeled cytoskeletal proteins in consecutive segments of the sciatic nerve and the ventral roots were fractionated into soluble and insoluble forms by extraction in 1% Triton at low temperature. In 4-week-old rats, the two forms of tubulin were transported coordinately in a single wave with the average rate of 2 mm/day. At 7 weeks of age, two components in tubulin transport were observed to develop, possibly reflecting the maturation of the axonal cytoskeleton. The slower main component (1.5 mm/day) contained most of the insoluble form together with the neurofilament proteins and the faster component (3 mm/day) was enriched in the soluble form. Though significantly different in composition, the two components correspond to slow component a (SCa) and slow component b (SCb) originally defined in the optic system. A progressive decrease in transport rates of both SCa and SCb was observed with rats at 14, 30, and 80 weeks of age. In addition, there was a large decrease in the proportion of insoluble tubulin during the course of transport in animals older than 30 weeks. This loss of the insoluble form seems to be accounted for partly by the proteolytic degradation of the severely retarded SCa proteins. Changes in axonal transport of tubulin may thus reflect age-related changes in dynamics and turnover of the axonal cytoskeleton.     

Altered genetic response to beta-adrenergic receptor activation in late passage C6 glioma cells.

Previous studies have demonstrated variability in the phenotype of rat C6 glioma cells. In the present study, we compared morphology, growth rate, and beta-adrenergic regulation of gene expression in early (P39-47) and late (P55-90) passage C6 cells. Morphological changes were observed in five independently derived, late passage populations. In four of the five, the untreated cells were more polygonal than the fibroblast-like parental cells, and only a small fraction exhibited process outgrowth after dbcAMP treatment. Untreated cells from the fifth late passage population had longer cytoplasmic processes than parental cells and responded to dbcAMP with further process outgrowth. All late passage populations had shorter generation times than the parental cells. In early passage cells, treatment with the beta-adrenergic agonist, isoproterenol (IPR), resulted in an increase in c-fos mRNA and a decrease in c-jun mRNA (Gu-bits RM, Yu H: J Neurosci Res, 30:625-630, 1991). Both of these immediate early gene responses were irreversibly lost between P50 and P55. Additional differences in basal or IPR-induced mRNA levels were observed for beta-APP, GFAP, NGF, and PPE, but not for a number of other mRNAs. These results are discussed in relationship to previously described differences in the ability of early and late passage C6 cells to accumulate cAMP (Mallorga P, et al.: Biochim Biophys Acta 678:221-229, 1981).     

Vasopressin stimulation of NaCl transport in the medullary thick ascending limb of Henle's loop is decreased in aging mice

The maximal urinary osmolality that can be reached by the kidney is reduced with age. This may be due to impaired NaCl transport by the medullary thick ascending limb of Henle's loop, which is part of the renal concentrating mechanism and is modulated by antidiuretic hormone (ADH). We therefore tested in vitro a possible age-related change in the transport capacity and in the response of this nephron segment to ADH in young (1–2 months) and old (20–24 months) mice. The transepithelial potential difference (V _te) was significantly higher in young mice (+8.5±0.4 mV, n=13) than in old ones (+6.6±0.5 mV, n=17). Addition of 0.1 nmol.l^–1 ADH to the bath solution significantly increased V _te by 5.2±0.5 mV in the young and by 3.1±0.6 mV in the old animals. Application of dibutyryl-cAMP (0.1 mmol.1^–1) did not further increase the hormonal response in both groups. The ADH-mediated increase in the corresponding equivalent short-circuit current (I _SC = V _te/R_te) was twice as great in young mice as in old, indicating that the stimulation of NaCl transport by ADH across the medullary thick ascending limb is significantly reduced with age. These results suggest that the previously reported age-related defect in the urinary concentrating ability of the kidney is partly due to a decreased response of the medullary thick ascending limb to ADH.     

1000例正常人发电子自旋共振（ESR）波谱的饱和特性研究

本文报道1000例正常人发自由基的电子自旋共振波谱饱和功率(ESR-SP)的检测结果。所得正常值的全组中位数为2.496mw;95％上下限分别为2.989及1.720mw。如按性别统计,则女性下限(1.617mw)较男性(1.983mw)为低,(P<0.05)。按年龄分别统计,则40岁以上的中位数(2.376mw)及其下限(2.009mw)高于40岁以下的中位数(2.548mw)及其下限(1.597mw),两者差异有显著性(P<0.05)及极显著性(P<0.01)。因此在使用此正常值指标时,必须注意性别与年龄因素。     

常温与低温体外循环心脏直视手术对细胞因子及补体的影响

目的探讨常温及低温体外循环心脏直视手术对细胞因子及补体的影响。方法选择先天性和风湿性心脏病患者40例,随机分为常温组及低温组各20例,分别于术晨、体外循环结束时及术后1、4、7、14 d抽取患者静脉血标本,测定血浆TNF、IL-2、C3、C4值。结果两组术前各项检查指标无显著差异。(1)两组术后1~4 d的IL-2水平较术前显著下降,至术后7 d恢复正常。体外循环结束至术后4 d,低温组IL-2显著低于常温组。(2)体外循环结束时以及术后1、4、7 d,常温组TNF水平显著低于低温组。两组体外循环结束时及术后1、4 d均高于术前,常温组至术后7 d、低温组术后14 d恢复正常。(3)体外循环结束时及术后1、7 d,常温组C3水平高于低温组,术后4 d两组无差别;常温组及低温组于体外循环结束时、术后1、4 d均低于术前,至术后7 d常温组恢复正常,低温组至术后14 d恢复至术前水平。(4)两组体外循环结束时及术后1、4 d C4水平均低于术前。体外循环结束时、术后1 d,常温组C4水平高于低温组。结论常温体外循环心脏直视手术对细胞因子及补体的影响显著轻于低温组,因而对术后机体的恢复优于低温方法。