神经节苷脂GM3在多囊卵巢综合征大鼠卵巢及卵泡中的定位研究

目的:探讨神经节苷脂GM3在多囊卵巢综合征大鼠卵巢发育过程中的表达及定位,为进一步研究神经节苷脂GM3在卵泡发育和排卵过程中的作用提供依据。方法:采用高性能薄层色谱分析法测定PCOS大鼠卵巢神经节苷脂GM3的表达;用免疫荧光激光共聚焦技术检测神经节苷脂GM3在PCOS大鼠的不同发育阶段卵泡中的表达及定位。结果:多囊卵巢综合征大鼠卵巢组织中提取的神经苷脂主要成分为GM3;与正常对照组相比,PCOS大鼠卵巢组织中神经苷脂GM3的表达水平显著降低。PCOS大鼠的初级卵泡、次级卵泡及窦状卵泡中的神经苷脂GM3的表达水平显著降低。结论:多囊卵巢综合征大鼠的卵巢发育过程中神经苷脂GM3的表达水平显著降低。提示,卵泡发育异常可能与GM3的表达程度密切相关。     

神经节苷脂与脑发育

神经节苷脂主要存在于中枢神经系统中,是神经细胞膜的重要结构成分和功能组分。它参与神经元的生长、突触的形成以及神经递质传递的调控,因此对大脑发育至关重要。孕期神经节苷脂随着胎儿脑发育在大脑中大量积累,出生后,依赖母乳提供的神经节苷脂支持脑和神经系统继续发育。动物模型及临床试验显示孕妇补充神经节苷脂有利于胎儿大脑发育。随机对照试验显示,配方粉中添加神经节苷脂可显著促进非母乳喂养儿的智力发育。关于母乳中神经节苷脂含量的分析及神经节苷脂对婴儿脑发育的研究还很少,有必要开展相关研究来探讨神经节苷脂在大脑发育过程中的作用。     

神经节苷脂治疗帕金森病的临床观察

目的观察神经节苷脂(GM1)治疗帕金森病的疗效。方法帕金森病60例,分为GM1组和对照组各30例。GM1组给予GM1100mg/日静滴,2周1个疗程;两组均给予左旋多巴25~50 mg,每日2~3次,每隔3~7日增加6.25mg至每日300 mg,分3~4次服用,共2周。治疗前与治疗后进行临床症状的Webster评分,并进行比较。结果两组比较,差异有显著性意义(P<0.05)。治疗后2周Webster评分与治疗前相比有显著性意义(P<0.01)。结论神经节苷脂治疗帕金森病有良好疗效,能缓解震颤,开关现象改善,自主运动增加,生活质量提高。     

神经节苷脂相关性格林-巴利综合征的研究进展

格林-巴利综合征(GBS)是一种自身免疫性疾病,由法国医生兰德里最早记载,由法国神经病学研究学者Cuillain、Barre和Strohl进行命名,是神经内科的常见疾病,发病机制暂未完全明确。神经节苷脂是一种鞘糖脂类,是神经元轴突的重要组成部分。国内外多项研究表明GBS的发病与抗神经节苷脂抗体有着密切联系。单唾液酸四己糖神经节苷脂(GM1)作为神经节苷脂的一个亚型,提取自猪脑,是神经内外科的常用药物,应用范围广,应用量较大。已有多项研究报道显示静脉点滴GM1后有引发GBS的情况。在此,拟总结讨论神经节苷脂及其抗体和神经节苷脂相关性GBS的研究进展。     

神经节苷脂对婴儿生长发育影响的研究进展

目的 综述神经节苷脂在母乳中的含量及其对婴儿早期生长发育的影响,为探讨神经节苷脂在婴幼儿配方食品中的强化补充提供科学依据。 方法 检索PubMed、Web of Science和CNKI数据库,收集相关文献。 结果 婴儿生长发育所需的神经节苷脂主要来源于母乳和婴儿配方粉,在生命早期的脑发育、认知能力发展和肠道免疫功能发育等方面发挥重要作用。 结论 神经节苷脂对婴儿的神经发育和肠道免疫发育至关重要,婴儿配方食品中神经节苷脂的添加对早产儿和人工喂养婴儿的早期发展具有潜在益处。     

神经节苷脂GM1＋黄芪注射液治疗困乏综合征疗效观察

目的观察神经节苷脂GM1＋黄芪注射液治疗困乏综合征的疗效及毒副作用。方法将困乏综合征患者122例随机分为实验组和对照组,其中实验组62例,对照组60例。实验组给予神经节苷脂GM1和黄芪注射液静滴,治疗1周;对照组给予复方氨基酸注射液（14AA）、维生素C和肌苷静滴,治疗1周。结果显效率实验组（45．2％）与对照组（18．3％）对比（Χ^2=10．14,P〈0．01）,差异有统计学意义;总有效率实验组（93．6％）与对照组（76．6％）对比（Χ^2=4．66,P〈0．05）,差异有统计学意义。可见实验组疗效明显优于对照组。结论神经节苷脂GM1和黄芪注射液能较好解除困乏综合征患者的症状,改善身体状况,提高工作学习效率,无明显毒副作用,值得推广。     

神经节苷脂治疗高危婴儿脑损伤疗效观察

目的：观察神经节苷脂（GM1）治疗高危婴儿脑损伤的疗效。方法：将40例患儿分为观察组（20例）和对照组（20例）,两组均给予高压氧、运动疗法,对照组加用胞二磷胆碱或脑蛋白水解物,观察组应用GM1,用统一标准评测治疗前后两组精神运动发育商（DQ）各项评分,比较两组间的疗效。结果：神经节苷脂组疗效明显高于对照组（P〈0．01）。结论：神经节苷酯治疗高危婴儿脑损伤疗效明显。     

神经节苷脂治疗新生儿缺氧缺血性脑病临床观察

目的 探讨神经节苷脂（GM1）治疗新生儿缺氧缺血性脑病（HIE）的疗效.方法 将58例缺氧缺血性脑病（HIE）患儿随机分为治疗组和对照组,均给予常规治疗,治疗组在此基础上应用神经节苷脂（GM1）,20 mg/次,1次/d,10～14 d为1个疗程.结果 治疗后治疗组总有效率938%,显著高于对照组的781%,差异有统计学意义（P〈005）.两组患儿神经症状恢复时间和NBNA评分经统计学处理,差异均具有统计学意义（P〈005）,治疗组疗效优于对照组.结论 神经节苷脂（GM1）治疗缺氧缺血性脑病（HIE）疗效好,能促进临床症状缓解,缩短病程,提高治愈率.     

单唾液酸神经节苷脂对铅暴露大鼠海马神经细胞生长抑素表达的干预作用

目的 研究单唾液酸神经节苷脂（GM1）对铅暴露大鼠海马神经细胞生长抑素（SS）的影响。方法 成年SD大鼠60只，随机分为三组：对照组、染铅组及GM1干预组，20只／组，40只染铅动物饮用0．1％的醋酸铅去离子水三个月，制成慢性染铅大鼠模型。GM1干预组腹腔注射GM1 50mg／kg，对照组和染铅组腹腔注射等量生理盐水，连续14d。采用免疫组化的方法测定大鼠海马细胞SS，观察铅暴露及GM1对其阳性表达的影响。结果 染铅组大鼠学习记忆能力较对照组明显减低，海马CA1区SS阳性神经元数量减少，差异有统计学意义（P〈0．05）；腹腔注射神经节苷脂后，Y-迷宫错误次数减少，其海马CA1区SS阳性神经元数量增多，差异有统计学意义（P〈0．05），CA1区SS阳性神经元数量亦增多但差异无统计学意义（P〉0．05）。结论 外源性神经节苷脂有可能增强海马细胞SS的阳性表达．从而一定程度的改善染铅大鼠的肇习记忆能力。     

神经节苷酯GM1、GM3在胃癌患者血清中的表达及意义

目的 探讨血清神经节苷酯GM1、GM3在胃癌患者血清中的表达及意义.方法 采用ELISA法检测40例胃癌患者血清中GM1和GM3的含量及与正常人血清神经节苷酯含量对比有无差异.结果 胃癌组血清GM1和GM3均较健康体检者明显升高[（815.53±75.56）ng/ml vs（88.88±32.73）ng/ml;（765.92±61.09）ng/ml vs（28.03±9.64）ng/ml,P〈0.01],胃癌患者经化疗后及手术后组与正常对照组差异无统计学意义（P〉0.05）.GM1与GM3两者之间呈正相关（r=0.24,P〈0.05）.结论 胃癌患者血清GLS显著增加;其测定对胃癌患者的早期诊断、疗效判定、复发预测具有显著临床价值.     

human and bovine milk gangliosides differ in their fatty acid composition

Gangliosides are considered bioactive components in human infant nutrition, and their fatty acid composition alters their biological effects. We used matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) MS and GLC to analyze the fatty acid composition of the predominant gangliosides, the monosialoganglioside GM(3) [sialic acid (Sia) alpha2-3 galactose (Gal) beta1-4 glucose (Glc) beta1-1 ceramide] and the disialoganglioside GD(3) (Sia alpha2-8 Sia alpha2-3 Gal beta1-4 Glc beta1-1 ceramide), in pooled human and bovine milk, the latter being a source for gangliosides in infant formula. Compared with whole milk lipids, both human and bovine milk gangliosides were selectively enriched with certain fatty acids, and the fatty acid composition of milk gangliosides in the 2 species was significantly different. The amount of long-chain fatty acids (> or =20 C atoms) was higher in bovine milk gangliosides (GM(3): 73.71 +/- 3.39%; GD(3): 79.19 +/- 2.79%) than in human milk gangliosides (GM(3): 51.25 +/- 0.65%; GD(3): 34.04 +/- 1.80%). Tricosanoic acid (23:0) dominated in bovine milk gangliosides (GM(3): 24.05 +/- 1.37%; GD(3): 26.66 +/- 1.24%), whereas it only played a minor role in human milk gangliosides (GM(3): 2.88 +/- 0.10%; GD(3): 1.84 +/- 0.29%). We hypothesized that the differences in the fatty acid composition of milk gangliosides result in physiological distinctions between breast-fed and formula-fed infants and therefore are of importance for human infant nutrition.     

Characterization and chronological changes of preterm human milk gangliosides

Objective

Gangliosides are present in high concentrations in the nervous tissue, and some are observed in small amounts in many extraneural tissues and body fluids. Human milk may play important roles in energy supplementation, prophylaxis of infection, and brain development. For preterm infants, human milk gangliosides are also very important substances during the early lactation stage. However, there are no data on human milk gangliosides from mothers at preterm delivery. We investigated the characterization of gangliosides and chronologic changes in human preterm milk earlier than 30 wk of gestation from 1 to 60 d after birth.

Methods

Forty-one samples were analyzed by high-performance thin-layer chromatography and a microtechnique using 1 mL of milk from each lactation and compared with 61 full-term human milk samples.

Results

Total lipid-bound sialic acid of human milk gangliosides after preterm delivery showed a peak concentration at 2 to 3 d postpartum and then remained at a high concentration until approximately 10 d. GD3 was the major ganglioside in the colostrum until approximately 7 to 10 d postpartum. GM3 was scarcely detected until 7 d postpartum and then increased gradually. There was no difference in the GD3 concentration per 1 mL of human milk between preterm and full-term human milk until approximately 5 to 8 d postpartum. After that time, the GD3 concentration decreased sharply. In contrast, the total concentrations of GM3 per 1 mL of human milk from mothers after preterm delivery were lower than those from mothers after full-term delivery throughout the entire period examined.

Conclusion

This finding is essential to elucidate the composition of human milk gangliosides after preterm delivery, which may contribute to the analysis of the physiologic composition and formulation appropriate preterm infant nutrition.     

Profiling gangliosides from milk products and other biological membranes using LC/MS

Gangliosides are an important class of glycosphingolipids involved in numerous biological processes such as neuronal development, host–pathogen interactions and gastrointestinal health. Due to the highly heterogeneous nature and relatively low abundance of gangliosides, characterization of gangliosides in biological membranes is challenging. Existing methods for ganglioside analysis are quite time consuming and require expensive high resolution mass spectrometers. A rapid method combining reversed phase chromatography and mass spectrometry was developed using a triple-quadrupole mass spectrometer operating in multiple reaction monitoring mode. The ganglioside species were separated with a Poroshell 120 EC-C18 column and analysed under the negative ion mode. This method allows a sensitive, specific, and quantitative assay for profiling gangliosides. The method is developed for analysis of gangliosides in the milk fat globule membrane of whole milk and applied to other biological membranes. Application includes the cellular membrane of prostate cancer cells. In summary, the method allows various biological membranes to be screened for over 600 gangliosides from 12 classes (GM1, GM2, GM3, GM4, GD1, GD2, GD3, GD4, GT1, GT2, GT3, and GT4) in less than three hours. In summary, expressed as % of relative amounts: 1.5% GM3, 80.2% GD3, 14.4% GT3, 1.5% GM1, 2.4% GD1 were observed in whole milk; 2.5% GD1, 88.2% GD3, 2.5% GM1, 2.2% GM3, 0.2% GT2, 4.2% GT3 were observed in buttermilk and 10.6% GD1, 55.6% GD3, 1.6% GM1, 12.2% GM3, 19.2% GT3, 0.9% GT4 were observed in colostrum.     

The role of dietary gangliosides on immunity and the prevention of infection

Gangliosides are acid glycosphingolipids widely distributed in most vertebrate tissues and fluids. They are present in mammalian milk, where they are almost exclusively associated with the membrane fraction of the fat globule. In human milk, the content and individual distribution of gangliosides changes during lactation, GD3 being the most abundant ganglioside in colostrum, while in mature milk, GM3 is the major individual species. Gangliosides function as "unintended" target receptors for bacterial adhesion in specific tissues. After oral administration, they can be putative decoys that interfere with pathogenic binding in the intestine, this being the main mechanism by which these compounds can prevent infection. Ganglioside-supplemented infant formula has been reported to modify the intestinal ecology of preterm newborns, increasing the Bifidobacteria content and lowering that of Escherichia coli. In addition, the influence of dietary gangliosides on several parameters related to the development of intestinal immune system, such as cytokine and intestinal IgA production, has also been described in animal models. Recently, the influence of GM3 and GD3 on dendritic cell maturation and effector functionalities has also been reported, suggesting a role for these milk gangliosides, especially GD3, in modulating the process of oral tolerance during first stages of life. In summary, dietary gangliosides may have an important role in the modification of intestinal microflora and the promotion of intestinal immunity development in the neonate, and consequently in the prevention of infections during early infancy.     

Effect of neonatal undernutrition on rat brain gangliosides

Effects of age and neonatal undernutrition were studied on total and fractions of gangliosides (GT1, GD1b, GD1a and GM1) in rat brain. GT1, GD1b + GD1a and GM1 are being presented here as polysialo-, disialo-, and monosialo-gangliosides. Undernutrition was induced by feeding mothers a low protein diet during lactation. The concentration of gangliosides increased to its maximum level by the age of 3 weeks and then decreased to its adult value by the age of 8 weeks. Polysialo gangliosides (GT1) comprised the maximum amount of gangliosides at birth (40%) and decreased to an adult value by 3 weeks of age. Disialo ganglioside GD1b increased to its maximum by 2 weeks and then leveled off. Disialo ganglioside GD1a and GM1 showed a decrease by 2 weeks and then reached to its adult value by 4 weeks. Neonatal undernutrition results in a decreased body and brain weight at all ages studied (7, 14 and 21 days) as well as total ganglioside concentration by 36%, 15% and 55% respectively at 7, 14 and 21 days. Polysialo gangliosides (GT1) constitute the major fraction of gangliosides at 21 days in undernourished rats as compared to controls, whereas mono- and di-sialo gangliosides remained decreased at all three ages compared to controls. This indicates the possibility of an underlying metabolic defect in undernourished animals.     

Ganglioside composition of differentiated Caco-2 cells resembles human colostrum and neonatal rat intestine

Gangliosides are glycosphingolipids found in cell membranes and human milk with important roles in cell proliferation, differentiation, growth, adhesion, migration, signalling and apoptosis. Similar changes in ganglioside composition occur during embryonic development, lactation and cancer cell differentiation. It is not known, however, whether ganglioside compositional changes that occur in differentiating colon cancer cells reflect changes that occur during intestinal development. The Caco-2 cell line is commonly used to study physiological and pathophysiological processes in the small intestine and colon. Therefore, to examine this question, undifferentiated and differentiated Caco-2 cells were grown and total lipid was extracted from cell supernatant fractions using the Folch method. The upper aqueous phase containing gangliosides was collected and purified. Total gangliosides were measured as ganglioside-bound N-acetyl neuraminic acid, while individual ganglioside content was quantified via a colorimetric assay for sialic acid and scanning densitometry. The total ganglioside content of differentiated Caco-2 cells was 2.5 times higher compared with undifferentiated cells. Differentiated Caco-2 cells had significantly more (N-acetylneuraminyl) 2-galactosylglucosyl ceramide (GD3) and polar gangliosides, and a lower N-acetylneuraminylgalactosylglucosylceramide (GM3):GD3 ratio than undifferentiated cells. The present study demonstrates that the total ganglioside content and individual ganglioside composition of differentiated Caco-2 cells are similar to those of human colostrum and neonatal rat intestine. Differentiated Caco-2 cells may therefore be an alternative model for studying physiological and pathological processes in the small intestine and colon, and may help to elucidate possible functions for specific gangliosides in development and differentiation. Further research using more sensitive techniques of ganglioside analysis is needed to confirm these findings.     

Modulation of ganglioside expression in human melanoma cell lines; increased resistance to chemo- and radiation treatment.

Cell surface gangliosides in human melanoma cell lines were modulated by pretreatment and adaptation to 6-thioguanine and 5-bromo-deoxyuridine. Chemo- and radiation sensitivities were compared in original cell lines and modulated cells by the human tumor colony-forming assay. Modulated cells showed decreased expression of cell surface GM2 and GD2 gangliosides. This reduction was correlated with increased resistance to bleomycin, vincristine, cisplatin and radiation treatment. These results suggest that cell surface GM2 and GD2 ganglioside expression in human melanoma cells is intimately associated with several cellular biological properties, such as drug or radiation sensitivity and cellular differentiation.     

Concentration and distribution of sialic acid in human milk and infant formulas

BACKGROUND: In animal studies, sialic acid supplementation is associated with increases of gangliosides in the brain and improved learning ability. Only limited data are available on the sialic acid content of human milk and infant formulas. OBJECTIVE: We compared the concentrations of oligosaccharide-bound, protein-bound, and free sialic acid in milk from mothers of full-term and preterm infants and in a range of infant formulas. DESIGN: The milk from 20 and 14 mothers of full-term and preterm infants (mean gestational age: 31 +/- 3 wk), respectively, was collected at 4 stages of lactation (colostrum, transition, 1 mo, and 3 mo) and compared with 21 different infant formulas. RESULTS: Total sialic acid concentrations were highest in colostrum (x +/- SEM: 5.04 +/- 0.21 mmol/L in full term) and decreased by nearly 80% over the next 3 mo. Human milk from mothers of preterm infants contained 13-23% more sialic acid than did milk from mothers of full-term infants at 3 of the 4 lactation stages (P < 0.02). The sialic acid content of most formulas was <25% of that found in mature human milk (P < 0.01). Most of the sialic acid in the formulas ( approximately 70%) was bound to glycoproteins, whereas in human milk most sialic acid was bound to free oligosaccharides. CONCLUSIONS: Human milk, including milk from mothers of preterm infants, is a rich source of oligosaccharide-bound sialic acid, which contrasts with the relatively small amounts found in infant formulas. The nutritional significance of sialic acid is presently unknown, but it is plausible that it is a conditional nutrient that contributes to sialic acid accretion in the brain.     

Negative calcium balance during lactation in rural Mexican women

BACKGROUND: Additional calcium is required during lactation, and several calcium regulatory factors are involved in calcium balance. In lactating rural women who have marginal nutrition and consume a high-fiber diet, negative calcium balance may be expected. OBJECTIVE: We evaluated calcium balance and its association with potential calcium regulatory factors in lactating, rural Mexican women who had marginal nutrition and consumed a high-fiber diet. DESIGN: This cross-sectional study included women at 1, 3, 6, and 12 mo of lactation (L1, L3, L6, and L12 groups) and women who had weaned their infants (W group). Age-matched, nonlactating women (NL group) were also included. Calcium balance and concentrations of calcium regulatory factors were determined. Correlation analysis was performed by using data from all of the lactating women. RESULTS: Calcium balance in the L1, L3, and L6 groups was negative and was significantly different (P < 0.05) from that in the W and NL groups. Serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] concentrations were significantly higher (P < 0.05) in the W group than in the L and NL groups. Calcium balance was positively associated with serum estradiol concentrations (r = 0.58, P < 0.05) and negatively associated with serum 1,25-(OH)(2)D concentrations (r = -0.52, P < 0.05). Breast-milk calcium concentrations correlated positively with serum PTH-related peptide (PTHrP) concentrations (r = 0.51, P < 0.05) and negatively with serum estradiol concentrations (r = -0.57, P < 0.05). CONCLUSIONS: Negative calcium balance was observed during lactation in rural Mexican women who consumed a high-fiber diet. Furthermore, the data suggest that the hormones estradiol and PTHrP are involved in the regulation of calcium balance and of the calcium content of milk during lactation.