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

Journal of Neuroinflammation

Pauline Roost¹  Caroline Jan¹  Emmanuel Brouillet¹  Nadja Van Camp¹  Francesco Gubinelli¹  Ana Lúcia Rebelo²  Abhay Pandit²  Radka Saldova³  Richard R. Drake⁴ 

[1] CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, Université Paris-Saclay, Fontenay-aux-Roses, France;CÚRAM SFI Research Centre for Medical Devices, National University of Ireland, Galway, Ireland;CÚRAM SFI Research Centre for Medical Devices, National University of Ireland, Galway, Ireland;National Institute for Bioprocessing Research and Training (NIBRT), University College Dublin, Dublin, Ireland;UCD School of Medicine, UCD Conway Institute of Biomolecular and Biomedical, Dublin, Ireland;Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, USA;

关键词: N;    Protein glycosylation;    Glycomics;    Neuroinflammation;    Striatum;    LPS model;    Liquid chromatography;    MALDI-MSI;   

DOI  :  10.1186/s12974-021-02163-6

来源: Springer

【 摘 要 】

BackgroundNeuroinflammation 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.MethodsWith 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).ResultsIn 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.ConclusionsTogether, 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.

【 授权许可】

CC BY