Human brain gangliosides in development, aging and disease.
In this study, brain gangliosides in prenatal and postnatal human life and Alzheimer's disease were analyzed. Immunohistochemically, the presence of the "c"-series of gangliosides (GQ1c) was only registered in the embryonic brain at 5 weeks of gestation. Biochemical results indicated a two-fold increase in ganglioside concentration in the human cortex between 16 and 22 weeks of gestation. The increasing ganglioside concentration was based on an increasing GD1a ganglioside fraction in all regions analyzed except in the cerebellar cortex, which was characterized by increasing GT1b. During prenatal human development, regional differences in ganglioside composition could only be detected between the cerebrum ("a"-pathway) and the cerebellum ("b"-pathway). Between birth and 20-30 years of age, a cerebral neocortical difference of ganglioside composition occurred, characterized by the lowest GD1a in visual cortex. Analyzing the composition of gangliosides in cortical regions during aging, they were observed to follow region-specific alterations. In the frontal cortex, there was a greater decrease in GD1a and GM1 than in GT1b and GD1b, but in the occipital (visual) cortex there was no change in individual gangliosides. In hippocampus, GD1a moderately decreased, whereas other fractions were stable. In the cerebellar cortex, GD1b and GT1b fractions decreased with aging. In Alzheimer's disease, we found all ganglio-series gangliosides (GM1, GD1a, GD1b, GT1b) to be decreased in regions (temporal and frontal cortex and nucleus basalis of Meynert) involved in pathogenesis of disease. In addition, in Alzheimer's disease we found simple gangliosides (GN2, GM3) to be elevated in the frontal and parietal cortex, which might correlate accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.
Kracun
I
I
Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, Republic of Croatia, Yugoslavia.
Rosner
H
H
Drnovsek
V
V
Heffer-Lauc
M
M
Cosović
C
C
Lauc
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D005732:Gangliosides / Q000032:analysis* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids / Q000032:analysis
D005732:Gangliosides; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid