Mapping and Sequencing of Gangliosides from Anencephaly by Electrospray Ionization High Capacity Ion Trap Mass Spectrometry

Abstract

Congenital malformation referred to as anencephaly is a neural tube defect that occurs when the cephalic end of the neural tube fails to close, resulting in the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain—the largest part of the brain consisting mainly of the cerebrum, which is responsible for thinking and coordination. Although some individuals with anencephaly may be born with a rudimentary brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. Gangliosides (GGs) are sialylated glycosphingolipids present in the cell plasma membrane, responsible for the modulation of the cell signal transduction events. GGs act as receptors of interferon, epidermal growth factor, nerve growth factor and are differently expressed in various pathological states of central nervous system (CNS) acting as biomarkers of CNS disorders. In this study a native GG mixture extracted and purified from a histopathologically-defined anencephalic fetal brain remnant was analyzed by electrospray ionization high capacity ion trap mass spectrometry. Structural data upon disease-associated species were collected by multiple stage collision-induced dissociation of the molecular ions. As a control a native GG mixture from a normal fetal brain in the same developmental stage was used. Comparative screening and sequencing revealed the differential expression of the GGs in aberrant vs. healthy tissue and provided accurate information upon the structure of several anencephaly-associated species.