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Identifier

000460267

Title

Investigation of the protective role of caloric restriction mimetics in myelin disruption : in vivo and in vitro approaches

Alternative Title

Διερεύνηση του προστατευτικού ρόλου μιμητών θερμιδικού περιορισμού στη διατάραξη της μυελίνης: in vivo and in vitro προσεγγίσεις

Author

Καφφέ, Δέσποινα Β.

Thesis advisor

Καραγωγέως, Δόμνα

Reviewer

Βιδάκη, Μαρίνα
Ταβερναράκης, Νεκτάριος

Abstract

Caloric restriction is defined as the reduction of food consumption without malnutrition and is considered as a physiological inducer of autophagy that attenuates demyelination and promotes remyelination. In this study we evaluated the effect of nicotinamide (NAM) and resveratrol (RSV), two well-known caloric restriction mimetics (CRMs), on myelin production upon demyelinating conditions as well as their direct effects on the glial populations of the central nervous system that interact during the process of remyelination. To address these questions we used a lysolecithin (LPC)-induced focal demyelination mouse model as well as primary cultures of microglia, oligodendrocytes and astrocytes. Preliminary data of our laboratory reveal that NAM results in increased MBP immunoreactivity along with reduced microgliosis and astrogliosis at the lesion site upon LPC-induced demyelination. Even though NAM does not directly affect the proliferation or differentiation of oligodendrocyte progenitor cells (OPCs), it influences both microglia and astrocytes. Specifically, NAM reduces the population of proinflammatory microglia and promotes the anti-inflammatory phenotype of astrocytes in vitro, an effect that is, at least in part, mediated by autophagy. Similarly, RSV enhances PLP density in the lesion site of LPC-demyelinated animals. However, it does not reduce the accumulation of astrocytes or microglia at the area of the lesion. In fact, there is a tendency of RSV to increase astrogliosis without affecting microglia accumulation. Regarding its cell-autonomous effects, RSV does not affect either the proliferation or the differentiation of OPCs, whereas it exerts ambiguous effects on the activation of microglia and astrocytes, affecting the intermediate phenotypes. Overall, our results indicate that both CRMs influence microglia and astrocytes directly, in favor of the remyelination process. Our data indicate that NAM promotes a less inflammatory microenvironment, whereas the effects of RSV on microglia and astrocytes are multifaceted and require further investigation.

Language

English

Subject

Astrocytes

Autophagy

Caloric restriction mimetics

Demyelination

Microglia

Nicotinamide

Oligodendrocytes

Remyelination

Resveratrol