engleski

Neuroplastin expression in the brain of ganglioside-deficient mice

Neuroplastin is a transmembrane glycoprotein belonging to the immunoglobulin (Ig) superfamily of cell adhesion molecules. It exists in two isoforms, np55 with two extracellular Ig domains and np65 with three extracellular Ig domains, Ig1 being specific for that brain-specific isoform. Neuroplastin has been shown to be involved in synaptic plasticity and neurite outgrowth. We found altered neuroplastin gene expression in a whole-genome expression analysis of ganglioside-deficient mice. Gangliosides, membrane glycosphingolipids crucial for proper functioning and maintenance of the nervous system, affect processes of neurite outgrowth, establish proper axon-myelin interactions and are involved in cell signaling. Increased neuroplastin gene expression in hippocampus and cerebellum of B4galnt1 null mice was confirmed by qRT-PCR. These mutant mice lack all complex gangliosides, instead synthesizing comparable amounts of simpler GM3 and GD3 structures. Additionally, Western blotting for hippocampus and cerebellum and immunohistochemical analysis of whole brain sections were performed using two neuroplastin antibodies which recognize Ig2-3 and Ig1-3 domains. The most striking differences in immunoreactivity were observed in the hippocampus of B4galnt1 null mice compared to wild type mice. Specifically, B4galnt1 null mice had relatively little neuroplastin immunoreactivity in the pyramidal layer of CA1 and CA2 whereas wild type mice had strong neuroplastin staining of pyramidal cells for both antibodies used. Changes in immunoreactivity were also found among layers of CA3 and dentate gyrus. Apart from the hippocampal formation, changes in immunoreactivity were found in frontal cortex and thalamus, although not as prominent. The thalamus of B4galnt1 null mice showed more dispersed neuroplastin immunoreactivity compared to wild type mice. In cerebellum no immunohistochemical changes in neuroplastin expression and localization were observed. These findings clearly show that neuroplastin expression is perturbed upon changed ganglioside environment of neural membranes. Further investigation should elucidate the exact interactions between gangliosides and neuroplastin in the mammalian nervous system.

neuroplastin; ganglioside-deficient mice

nije evidentirano