engleski

Dynamic changes in the N-glycome of the rat neocortex throughout ontogeny

Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth, and axon targeting. However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult. The aim of this study, therefore, was to perform a thorough characterization of N- glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment. To this end, we used hydrophilic interaction ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of- flight mass spectrometry to compare the adult neocortical Nglycome with that of 24 h and 48 h neonates. While the basic features of all the neocortical N-glycoprofiles were generally similar, we discovered numerous quantitative and qualitative differences in the composition of the N-glycomes. We report that the abundance of complex N-glycans is significantly lower in adults compared to neonates. Furthermore, the proportion of charged complex N-glycans is also greatly reduced. This decrease in the abundance of complex Nglycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N- glycans. Lastly, we report that although the proportion of total oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult. In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared to adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures. More broadly, our data suggest that the glycosylation requirements of the neocortex vary throughout brain development and that the neuroglycome is dynamic and adapts accordingly.

N-glycans ; N-glycosylation : brain ; neuroglycome ; neurodevelopment

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