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Identifier

000452163

Title

Investigation of the role of a caloric restriction mimetic in central nervous system remyelination using in vitro, ex vivo and in vivo approaches

Alternative Title

Διερεύνηση του ρόλου ενός μιμητή του θερμιδικού περιορισμού στην επαναμυελίνωση στο κεντρικό νευρικό σύστημα χρησιμοποιώντας in vitro, ex vivo και in vivo τεχνικές

Author

Λυγεράκη, Ανδριανή Ι.

Thesis advisor

Καραγωγέως, Δόμνα

Reviewer

Χαραλαμπόπουλος, Ιωάννης
Ταβερναράκης, Νεκτάριος

Abstract

Central nervous system (CNS) myelination is characterized by the formation of myelin sheaths around axons. Myelin disruption, termed demyelination, impairs signal conduction and axonal integrity, leading to neurodegeneration. Remyelination is a homeostatic mechanism that includes the formation of new myelin sheaths around demyelinated axons; yet this process is often compromised. Recently, there has been evidence suggesting that autophagy is essential in CNS myelin formation and maintenance, thus enhancement of autophagy could possibly contribute to remyelination. The most physiological inducer of autophagy is caloric restriction (CR). In this study we investigated the effect that a CR mimetic, particularly resveratrol (RSV), has on remyelination upon lysolecithin (LPC)-induced demyelination ex vivo and in vivo. Our results provide evidence that RSV enhances and accelerates remyelination. Regarding its mechanism of action, in vitro studies demonstrate that RSV directly promotes oligodendrocyte (OL) differentiation, likely through an autophagy-mediated way. Although OLs are the myelin-producing cells in the CNS, their development is affected by other glial populations present in their microenvironment. Our data propose that RSV accelerates the accumulation of astrocytes upon LPC-induced demyelination in vivo. Regarding microglia, RSV does not affect their accumulation in vivo; however more studies will take place in order to clarify its effect on this cell population. Taken together our study reveals the remyelinating effect of RSV upon LPC-induced demyelinating conditions ex vivo and in vivo. Further studies will take place in order to elucidate the mechanism of action of RSV and the requirement of autophagy in its effects towards the enhancement of remyelination. All in all our study suggests RSV as a potential therapeutic agent against demyelinating diseases and highlights the complex interplay of glial populations regarding the modulation of myelin homeostasis.

Language

English

Subject

Astrocytes

Demyelination

Microglia

Myekub

Oligondrocytes

Resveratrol

Απομυελίνωση

Αστροκύτταρα

Μικρογλία