Molecular Microscopy of Brain Gangliosides: Illustrating their Distribution in Hippocampal Cell Layers

Gangliosides are amphiphilic molecules found in the outer layer of plasma membranes of all vertebrate cells. They play a major role in cell recognition and signaling and are involved in diseases affecting the central nervous system (CNS). We are reporting the differential distribution of ganglioside species in the rat brain's cerebrum, based on their ceramide associated core, and for the first time the presence of acetylation detected by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, which was used to map and image gangliosides with detailed structural information and histological accuracy. In the hippocampus, localization of the major species GM1, GD1, O-acetylGD1, GT1, and O-acetylGT1 depends on the sphingoïd base (d18:1 sphingosine or d20:1 eïcosasphingosine) in the molecular layer of the dentate gyrus (ML), which is made up of three distinct layers, the inner molecular layer (IML), which contains sphingosine exclusively, and the middle molecular layer (MML) and the outer molecular layer (OML) where eïcosasphingosine is the only sphingoïd base. These results demonstrate that there is a different distribution of gangliosides in neuronal axons and dendrites depending on the ceramide core of each layer. GM3, GM2, GD3, and GD2 contain sphingosine predominantly and are mainly present in body cell layers, which are made up of the pyramidal cell layer (Py) and the granular layer of the dentate gyrus (GL), in contrast with GQ1 and the O-acetylated forms of GD1, GT1, and GQ1 gangliosides, which contain both sphingoïd bases. However their distribution is based on the sialylated and acetylated oligosaccharide chains in the neuronal cell bodies.