Neuroprotective effect of extracellular vesicles obtained from human glial derivatives on the model of glutamate excitotoxicity

Abstract

Relevance. Modern research in the field of biomedicine leads to the development of therapeutic drugs based on extracellular vesicles, which are defined as sources of production, as well as targeted modification. In the presented work, for the first time, transcriptome profiling of primary culture of cortical neurons under the influence of extracellular vesicles obtained from glial cells during glutamate excitotoxicity was carried out in order to determine differentially expressed genes. Materials and Methods. Extracellular vesicles were obtained from the conditioned medium of human glial progenitor cells using ultracentrifugation. Model of glutamate excitotoxicity, distributed on the first cultured cortical neurons of cells (P0) with the addition of 100 μM glutamate. Sequencing of prepared libraries of electronic technologies on the NextSeq 1000 platform (Illumina, USA) using the NextSeq 1000/2000 P2 (200 cycles) v3 reagent kit supplemented with 2 % Phix (Illumina) as an internal control. The criterion for statistical innovation of gene expression change between officially recognized FDR 0.05. Results and Discussion. Transcriptome analysis showed that the addition of extracellular vesicles during glutamate excitotoxicity leads to increased expression of 190 genes and decreased expression of 309 genes (p value 0.05 and |FC| 1.5). Gene analysis using the Gene Onthology database showed that genes with increased expression are consistently classified by biological processes. The most represented were: regeneration, reorganization of the extracellular matrix and cytoskeleton, maintenance of homeostasis, activation of the PI3K-Akt pathway and response to cellular stress. Genes with reduced expression were consistently classified into groups: calcium transport, regulation of neuronal processes, apoptosis, glutathergic synapse. These data can indicate that. Extracellular vesicles trigger survival processes in nerve cells when exposed to glutamate and inhibit pathways associated with the entry of substances and glutamate into the cell. Conclusions. Extracellular vesicles enhance the expression of genes with survival and inhibit genes, resulting in calcium transport and apoptosis. The results of the study show the promise of using extracellular vesicles of glial origin as a basis for developing new therapeutic approaches to individual neurological diseases.