| Abstract |
Autophagy is a catabolic process that mediates the clearance of cytoplasmic constituents through a variety of pathways (i.e., chaperone-mediated autophagy, micro-autophagy, macro-autophagy). Macro-autophagy has recently drawn the attention of researchers due to its potential contribution to the normal function of Oligodendrocytes (OLs), the myelinating glia of the Central Nervous System (CNS). On a functional level, OLs are responsible for both the formation of new myelin and the maintenance of existing myelin in the CNS. Of particular interest is the fact that OL-lineage cells and by extension myelination display sexual dimorphism during adulthood. Taking into account that the relationship between macro-autophagy and CNS myelination is an intriguing research concept that has yet to be fully elucidated, the aim of this study was to examine the significance of a well-regulated macro-autophagic mechanism for the maintenance of myelin homeostasis in the adult mouse brain and to identify whether there is a sexually dimorphic effect of basal autophagy on CNS myelin during the respective period. For this purpose, we ablated the macro-autophagic pathway (through deletion of ATG5), specifically in OLs of adult male and female mice, and examined the results of that blockade three months later on a cellular, structural and behavioral level. According to the respective results, cKO males displayed higher levels of PLP, axons with smaller g-ratios, increased density of axons with myelin decompaction, high levels of axonal degeneration and motor-learning deficiencies. Female mice, on the other hand, were characterized only by an increase in the number of axons with decompacted myelin. Overall, our data confirmed not only the contribution of the macro-autophagic pathway in the maintenance of normal myelination in the adult CNS of both males and females, but also a sexually dimorphic effect in the respective process.
|
Sexual dimorphic effects in the absence of autophagy in CNS myelin
