Recently, D-aminoacids are emerging as molecules with important roles in glial cells. Among them, D- aspartate (D-Asp), plays a relevant role during nervous system development and in the neuroendocrine system. The observation that D-Asp is present in considerable levels in the white matter and it may influence glutamate receptor signaling was what led us to investigate the effects of D-Asp treatment on oligodendrocytes both in vitro, during OPC differentiation, and in vivo, in mice fed with the copper chelator cuprizone. Quantitative RT-PCR analyses show that 10-200 µM D-Asp exposure upregulated, in a concentration- dependent manner, both the myelin markers CNPase and MBP and NCX3 transcripts in human oligodendrocytes M03.13 progenitors after 3 days. The transcripts increase were significantly prevented by the NMDA receptor antagonist 10 µM MK-801 and the two NCX3 blockers, 30nM YM-244769 and 100nM BED. Fura-2 video-imaging showed that either MK-801, or YM-244769 and BED significantly suppressed [Ca 2+ ] i oscillations induced by D-Asp exposure both in MO3.13 oligodendrocytes and primary rat OPC. In vivo, D-Asp was given during cuprizone feeding, or after cuprizone withdrawal. In both conditions, D-Asp treatment significantly improved motor performance, as assessed with the beam balance and rotarod tests. D-Asp treatment during demyelination significantly prevented the loss of MBP expression and the increase in Iba1 and GFAP levels as revealed by Western Blot and confocal immunofluorescence analyses. Finally, electron microscopy performed on corpus callosum sections show that D-Asp treatment accelerates remyelination in cuprizone mice, as demonstrated by the increased number in myelinated axons if compared to untreated cuprizone mice. Collectively, our results show that treatment with D-Aspartate, by influencing calcium signaling in oligodendrocytes, might produce beneficial effects during demyelination and remyelination processes
Effects of D-aspartate on oligodendrocytes during differentiation, demyelination and remyelination processes / de Rosa, V.; Secondo, A.; Pannaccione, Anna; Ciccone, R.; Formisano, L.; Guida, N.; Crispino, R.; D'Aniello, A.; Polishchuk, R.; F. Boscia, L. Annunziato. - In: GLIA. - ISSN 1098-1136. - 65:S1(2017), p. E540. (Intervento presentato al convegno 13th European Meeting on Glial Cells in Health and Disease tenutosi a Edinburgh, SCOTLAND).
Effects of D-aspartate on oligodendrocytes during differentiation, demyelination and remyelination processes
A. Secondo;A. Pannaccione;R. Ciccone;L. Formisano;N. Guida;
2017
Abstract
Recently, D-aminoacids are emerging as molecules with important roles in glial cells. Among them, D- aspartate (D-Asp), plays a relevant role during nervous system development and in the neuroendocrine system. The observation that D-Asp is present in considerable levels in the white matter and it may influence glutamate receptor signaling was what led us to investigate the effects of D-Asp treatment on oligodendrocytes both in vitro, during OPC differentiation, and in vivo, in mice fed with the copper chelator cuprizone. Quantitative RT-PCR analyses show that 10-200 µM D-Asp exposure upregulated, in a concentration- dependent manner, both the myelin markers CNPase and MBP and NCX3 transcripts in human oligodendrocytes M03.13 progenitors after 3 days. The transcripts increase were significantly prevented by the NMDA receptor antagonist 10 µM MK-801 and the two NCX3 blockers, 30nM YM-244769 and 100nM BED. Fura-2 video-imaging showed that either MK-801, or YM-244769 and BED significantly suppressed [Ca 2+ ] i oscillations induced by D-Asp exposure both in MO3.13 oligodendrocytes and primary rat OPC. In vivo, D-Asp was given during cuprizone feeding, or after cuprizone withdrawal. In both conditions, D-Asp treatment significantly improved motor performance, as assessed with the beam balance and rotarod tests. D-Asp treatment during demyelination significantly prevented the loss of MBP expression and the increase in Iba1 and GFAP levels as revealed by Western Blot and confocal immunofluorescence analyses. Finally, electron microscopy performed on corpus callosum sections show that D-Asp treatment accelerates remyelination in cuprizone mice, as demonstrated by the increased number in myelinated axons if compared to untreated cuprizone mice. Collectively, our results show that treatment with D-Aspartate, by influencing calcium signaling in oligodendrocytes, might produce beneficial effects during demyelination and remyelination processesI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
