Anencephaly: Structural characterization of gangliosides in defined brain regions

Gangliosides from histopathologically-defined human cerebrum-resembling rem nant and cerebellum from 37 and 30 gestational week-old anencephaluses were identified using mass spectrometry and high performance thin layer chromat ography combined with immunochemical analysis in comparison to respective n ormal newborn/fetal and adult brain regions. A novel strategy of nano-elect rospray ionization quadrupole time-of-flight tandem MS has been developed f or identification of ganglioside components in complex mixtures. By morphoa natomical and histological investigation the anencephalic cerebral remnant was found to be aberrant, while the anencephalic cerebellum was defined as normal. Total ganglioside concentrations in the anencephalic cerebral remna nt and the cerebellum were 34% and 13% lower in relation to the age-matched controls. In the cerebral remnant, GD3, GM2 and GT1b were elevated, while GD1a was decreased in the anencephalic cerebral remnant, but enriched in an encephalic cerebellum. GQ1b was reduced in both anencephalic regions. Gg(4) Cer, GM1b and GD1 alpha, members of the alpha -series biosynthetic pathway, and neolacto-series gangliosides were found to be present in anencephalic, as well as in normal, fetal and adult brain tissues, indicating the occurr ence of these biosynthetic pathways in human brain. In both cerebral and ce rebellar anencephalic tissues, GM1b, GD1 alpha, nLM1 and nLD1 were expresse d at a higher rate in relation to normal tissue. It can be demonstrated tha t the anencephalic cerebral remnant, as a primitive brain structure, repres ents a naturally-occurring model to study the ganglioside involvement in in duction of aberrant brain development.