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Neuroplastin and ganglioside expression in human amygdala and hippocampus in temporal epilepsy

Neuroplastin (Np) is a transmembrane glycoprotein from the immunoglobulin superfamily. Due to alternative mRNA splicing it occurs in two isoforms one of which, neuroplastin-65 (Np65) is brain specific. Most of the current knowledge about neuroplastin has been obtained from studies in the murine brain, which have shown involvement of neuroplastin in neurite outgrowth, regulation and function of synapses, synaptic plasticity and associative memories formation. However, systematic data on neuroplastin expression and function in human brain are lacking. A few studies of neuroplastin in humans indicate association of Np gene polymorphisms with cognitive functions. Our study also showed changes in neuroplastin expression in human hippocampal samples affected by sporadic Alzheimer's disease and in mouse brain with mutations for familial Alzheimer’s disease. Previous research from our group has shown that the expression and immunopattern of neuroplastin in hippocampus depends on specific brain ganglioside composition. Gangliosides, sialic acid-bearing glycosphingolipids, are ubiquitous cell surface molecular determinants. However, they are predominant in mammalian brain where four complex gangliosides are most abundant: GM1, GD1a, GD1b, and GT1b. Gangliosides have important roles in modulating signal transduction, adhesion and cellular recognition and correct positioning and function of specific membrane proteins. Altered neuroplastin submembrane positioning caused by different membrane ganglioside composition implies a potential interplay between gangliosides and neuroplastin. Aim of this study was to determine expression of neuroplastin-65 and ganglioside pattern in human amygdala and hippocampal tissue affected by drug- resistant temporal epilepsy. Amygdala and hippocampal tissue samples were collected with previous patients’ informed consent and hospital ethical permission, during hippocampectomy in six patients with drug- resistant temporal epilepsy. Proteins were isolated from tissue homogenates and Np expression was analyzed by Western blotting. We also isolated and analyzed gangliosides from amygdala and hippocampal tissue using high- performance thin- layer chromatography (HPTLC). In addition, we performed immunohistological staining of neuroplastin in control sections of human amygdala. We report altered expression of the Np65 isoform in sclerotic hippocampal tissue compared to surrounding non-sclerotic control hippocampal tissue. These results show, for the first time, altered Np expression in sclerotic focus of temporal epilepsy in hippocampal tissue. Additionally, we present immunopattern of Np65 in control human amygdala.

neuroplastin ; gangliosides ; epilepsy ; amygdala ; hippocampus

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