التفاصيل البيبلوغرافية
| العنوان: |
Changes in glial cell activation and extracellular vesicles production precede the onset of disease symptoms in transgenic hSOD1G93A pigs. |
| المؤلفون: |
Golia, Maria Teresa1 (AUTHOR), Frigerio, Roberto1,2 (AUTHOR), Pucci, Susanna1 (AUTHOR), Sironi, Francesca3 (AUTHOR), Margotta, Cassandra3 (AUTHOR), Pasetto, Laura3 (AUTHOR), Testori, Camilla4 (AUTHOR), Berrone, Elena4 (AUTHOR), Ingravalle, Francesco4 (AUTHOR), Chiari, Marcella2 (AUTHOR), Gori, Alessandro2 (AUTHOR), Duchi, Roberto5 (AUTHOR), Perota, Andrea5 (AUTHOR), Bergamaschi, Luca5 (AUTHOR), D'Angelo, Antonio6 (AUTHOR), Cagnotti, Giulia6 (AUTHOR), Galli, Cesare5 (AUTHOR), Corona, Cristiano4 (AUTHOR), Bonetto, Valentina3 (AUTHOR), Bendotti, Caterina3 (AUTHOR) |
| المصدر: |
Experimental Neurology. Apr2024, Vol. 374, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*NEUROGLIA, *EXTRACELLULAR vesicles, *SYMPTOMS, *AMYOTROPHIC lateral sclerosis, *MOTOR neurons |
| مستخلص: |
SOD1 gene is associated with progressive motor neuron degeneration in the familiar forms of amyotrophic lateral sclerosis. Although studies on mutant human SOD1 transgenic rodent models have provided important insights into disease pathogenesis, they have not led to the discovery of early biomarkers or effective therapies in human disease. The recent generation of a transgenic swine model expressing the human pathological hSOD1G93A gene, which recapitulates the course of human disease, represents an interesting tool for the identification of early disease mechanisms and diagnostic biomarkers. Here, we analyze the activation state of CNS cells in transgenic pigs during the disease course and investigate whether changes in neuronal and glial cell activation state can be reflected by the amount of extracellular vesicles they release in biological fluids. To assess the activation state of neural cells, we performed a biochemical characterization of neurons and glial cells in the spinal cords of hSOD1G93A pigs during the disease course. Quantification of EVs of CNS cell origin was performed in cerebrospinal fluid and plasma of transgenic pigs at different disease stages by Western blot and peptide microarray analyses. We report an early activation of oligodendrocytes in hSOD1G93A transgenic tissue followed by astrocyte and microglia activation, especially in animals with motor symptoms. At late asymptomatic stage, EV production from astrocytes and microglia is increased in the cerebrospinal fluid, but not in the plasma, of transgenic pigs reflecting donor cell activation in the spinal cord. Estimation of EV production by biochemical analyses is corroborated by direct quantification of neuron- and microglia-derived EVs in the cerebrospinal fluid by a Membrane Sensing Peptide enabled on-chip analysis that provides fast results and low sample consumption. Collectively, our data indicate that alteration in astrocytic EV production precedes the onset of disease symptoms in the hSODG93A swine model, mirroring donor cell activation in the spinal cord, and suggest that EV measurements from the cells first activated in the ALS pig model, i.e. OPCs, may further improve early disease detection. [Display omitted] • Early activation of oligodendrocytes followed by astrocytes and microglia is detected in the spinal cord tissue of Tg hSODG93A pigs. • Astrocytes and microglia activation is reflected by elevated amounts of EVs derived by these cells in the CSF but not plasma. • Membrane Sensing Peptide measurements of glial EVs in small amount of unprocessed CSF samples may help early ALS diagnosis. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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