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Article Dans Une Revue Journal of Neuroinflammation Année : 2021

Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain

Résumé

Background Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended. A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure). N- glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation. Changes in N- glycosylation can ultimately affect glycoproteins’ functions, which will have an impact on cell machinery. Therefore, characterisation of N- glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies. Methods With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation. In vivo and post-mortem , quantitative and spatial characterisation of both neuroinflammation and N- glycome was performed at 1-week post-injection of LPS. These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI). Results In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N- glycans were significantly increased (13.5%). This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N- glycans, allowing precise comparison between normal and diseased brain hemispheres. Conclusions Together, our data show for the first time the complete profiling of N- glycomic changes in a well-characterised animal model of neuroinflammation. These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.
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cea-04470933 , version 1 (21-02-2024)

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Ana Lúcia Rebelo, Francesco Gubinelli, Pauline Roost, Caroline Jan, Emmanuel Brouillet, et al.. Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain. Journal of Neuroinflammation, 2021, 18 (1), pp.116. ⟨10.1186/s12974-021-02163-6⟩. ⟨cea-04470933⟩
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