Human brain gangliosides: developmental changes from early fetal stage to advanced age

Svennerholm, Lars; Boström, Kerstin; Fredman, Pam; Månsson, Jan‐Eric; Rosengren, Birgitta; Rynmark, Britt-Marie

doi:10.1016/0005-2760(89)90175-6

Cited by 263 publications

(185 citation statements)

References 46 publications

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“…The retinoic acid-induced alterations in the ganglioside complement of NB cells seem to reflect, therefore, a specific effect on ganglioside anabolism, although, theoretically, alterations in ganglioside catabolism or shedding are also possible contributing factors. Increased expression of complex gangliosides is a well-described feature of normal embryonic neurogenesis and accelerated axonogenesis (Svennerholm et al, 1989;Hirschberg et al, 1996). Similar ganglioside changes to those we describe here have been reported in retinoic acid-treated Xenopus embryo cells, murine embryonal carcinoma cells and SHSY-5Y NB cells during neuronal maturation (Rebhan et al, 1994;Rizzo et al, 1995;Liour et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

et al. 2004

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Recent findings link increased expression of the structurally complex 'b' pathway gangliosides GD1b, GT1b, GQ1b (CbG) to a favourable clinical and biological behaviour in human neuroblastoma (NB). Seeking a model to probe these observations, we evaluated four human NB cell lines. Very low CbG content (4 -10%) in three of the four cell lines (LAN-5, LAN-1, SMS-KCNR) reflected the ganglioside pattern observed in the most aggressive NB tumours. Pharmacological alterations of complex ganglioside synthesis in vitro by a 5 -7 day exposure to 5 -10 mM retinoic acid, which is employed in maintenance therapy of disseminated NB, included markedly increased (i) relative expression of CbG (6.672.0-fold increase, P ¼ 0.037), (ii) relative expression of the analogous 'a' pathway gangliosides, termed CaG (6.471.4-fold increase in GM1a and GD1a; P ¼ 0.010), and (iii) total cellular ganglioside content (2.0 -6.3-fold), which in turn amplified the accumulation of structurally complex gangliosides. Substantial increases (2.7 -2.9-fold) in the activity of GD1b/GM1a synthase (b-1,3-galactosyltransferase), which initiates the synthesis of CbG and CaG, accompanied the all-trans retinoic acid (ATRA)-induced ganglioside changes. Thus, increased CbG synthesis in NB cell lines is attributable to a specific effect of ATRA, namely induction of GD1b/GM1a synthase activity. Since the shift towards higher expression of CbG and CaG during retinoic acid-induced cellular differentiation reflects a ganglioside pattern found in clinically less-aggressive tumours, our studies suggest that complex gangliosides may play a role in the biological and clinical behaviour of NB.

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Section: Discussionmentioning

confidence: 99%

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

et al. 2004

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“…The rank order of decreasing brain sialic acid after humans was rat, mouse, rabbit, sheep, cow, and pig. In a 2-y-old chimpanzee, the brain cortex sialic acid concentration (Wang et al, 1998) was about one-third of the level of a human infant of the same age (Svennerholm et al, 1989). Also, the sialic acid concentration in left lobe of the brain cortex was 22% higher than that of the right lobe (Wang et al, 1998), possibly because the different brain regions perform different neurological functions (Suzuki, 1965).…”

Section: Figurementioning

confidence: 93%

“…The concentration increases approximately three times from the 10th gestational week to the age of about 5 y. Ganglioside GM1 and GD1a increase 12-15 times during the same period. GT1b is the major ganglioside during the third to fifth gestational month, thereafter its concentration drops rapidly to term, and then increases again up to 50 y of age (Svennerholm et al, 1989). There are also significant regional differences in the gangliosides patterns (Suzuki, 1965;Kracun et al, 1984).…”

Section: Sialic Acid In Brain Gangliosidesmentioning

confidence: 98%

“…Human milk sialic acid is highest during early lactation, a time when the brain is taking up sialic acid most rapidly (Svennerholm et al, 1989). In addition, deficits in protein or energy in rats during gestation are associated with decreased ganglioside sialic acid in the offspring and poor learning behaviour (Morgan & Naismith, 1982).…”

Section: Digestion and Absorption Of Sialic Acidmentioning

confidence: 99%

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The role and potential of sialic acid in human nutrition

2003

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Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins. In the human body, the highest concentration of sialic acid (as N-acetylneuraminic acid) occurs in the brain where it participates as an integral part of ganglioside structure in synaptogenesis and neural transmission. Human milk also contains a high concentration of sialic acid attached to the terminal end of free oligosaccharides, but its metabolic fate and biological role are currently unknown. An important question is whether the sialic acid in human milk is a conditional nutrient and confers developmental advantages on breast-fed infants compared to those fed infant formula. In this review, we critically discuss the current state of knowledge of the biology and role of sialic acid in human milk and nervous tissue, and the link between sialic acid, breastfeeding and learning behaviour.

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“…Specific neuronal ganglioside levels vary during embryogenesis but also in postnatal phases, especially during ageing (Ando, 1983;Aydin et al, 2000;Malisan and Testi, 2002;Ngamukote et al, 2007;Svennerholm et al, 1989;Yamamoto et al, 2008). Gangliosides seem to become increasingly important upon ageing, as late-onset and progressive histological and behavioural abnormalities develop in both GM2/GD2-synthase knockout (GM2s-KO) mice and compound null-mutant mice lacking GM2/GD2-and GD3-synthase.…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

Zitman

Todorov

Verschuuren

et al. 2011

Neurobiology of Aging

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Gangliosides are sialylated glycosphingolipids that are present in high density on neuronal membranes, especially at synapses, where they are assumed to play functional or modulating roles. Mice lacking GM2/GD2-synthase express only the simple gangliosides GD3 and GM3 and develop progressive motor behaviour deficits upon ageing, apparently due to failing complex ganglioside-dependent maintenance and/or repair processes or, alternatively, toxic GM3/GD3 accumulation. We investigated the function of neuromuscular junctions (NMJs) of aged (>9 months-old) GM2/GD2-synthase null-mutant mice, because synaptic dysfunction might develop with age and could potentially contribute to the late-onset motor phenotype. In addition, we studied NMJs of old mice lacking GD3-synthase (expressing only O-and aseries gangliosides), which do not show an overt neurological phenotype but may develop subclinical synaptic deficits. Detailed electrophysiological analyses showed subtle changes in presynaptic neurotransmitter release. Acetylcholine release at 40 Hz nerve stimulation at aged GM2/GD2-synthase null-mutant NMJs ran down slightly more pronounced than at wild-type NMJs, and spontaneous acetylcholine release rate at GD3-synthase null-mutant NMJs was somewhat higher than at wild-type, selectively at 25 C bath temperature. Interestingly, we observed faster kinetics of postsynaptic electrophysiological responses at aged GD3-synthase null-mutant NMJs, not previously seen by us at NMJs of young GD3-synthase null-mutants or other types of (aged or young) ganglioside-deficient mice. These kinetic changes might reflect a change in postsynaptic acetylcholine receptor behaviour. Our data indicate that it is highly unlikely that transmission failure at NMJs contributes to the progressive motor defects of aged GM2/GD2-synthase null-mutants and that, despite some kinetic changes of synaptic signals, neuromuscular transmission remains successful in aged GD3-synthase null-mutant mice. Apparently, mutual redundancy of the different gangliosides in supporting presynaptic function, as observed previously by us in young mice, remains adequate upon ageing or, alternatively, gangliosides have only relatively little direct impact on neuromuscular synaptic function, even in aged mice. AbbreviationsACh, acetylcholine; AChR, acetylcholine receptor; EPP, endplate potential; GD3s-KO, α2,8-sialyltransferase knockout; GM2s-KO, β1,4-GalNAc-transferase knockout; MEPP, miniature endplate potential; NMJ, neuromuscular junction; WT, wild-type.Zitman et al., Synaptic function in aged ganglioside-deficient mice 3

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Human brain gangliosides: developmental changes from early fetal stage to advanced age

Cited by 263 publications

References 46 publications

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

Alterations in neuroblastoma ganglioside synthesis by induction of GD1b synthase by retinoic acid

The role and potential of sialic acid in human nutrition

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

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