Altered N-linked glycosylation in depression: A pre-clinical study

• Published in: Journal of affective disorders 2024-08, Vol.359, p.333-341
• Main Authors: Yang, Yao, Li, Yuan, Wang, Wei-Di, He, Shen, Yuan, Ti-Fei, Hu, Ji, Peng, Dai-Hui
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Chronic unpredictable mild stress; Depression; Depression - metabolism; Depressive Disorder, Major - metabolism; Disease Models, Animal; Galactosyltransferases - genetics; Galactosyltransferases - metabolism; Glycosylation; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - metabolism; N-linked protein glycosylation; Stress, Psychological - immunology; Stress, Psychological - metabolism
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2024.05.118

Neuroimmune plays an important role in major depressive disorders (MDD). N-linked protein glycosylation (NLG) might contribute to depression by regulating the neuroinflammatory response. As microglia is the main executor of neuroimmune function in the central neural system (CNS), targeting the process of N-linked protein glycosylation of microglia in the mice used for studying depression might potentially offer new avenues for the strategy for MDD. The chronic unpredictable mild stress (CUMS) mouse model was established for the whole brain microglia isolating. Then, RNA samples of microglia were extracted for transcriptome sequencing and mRNA analysis. Immunofluorescence (IF) was used to identify the expression level of NLG-related enzyme, B4galt1, in microglia. The data showed that NLG was positively related to depression. Moreover, the NLG-related gene, B4galt1 increased expression in the microglia of CUMS mice. Then, the inhibition of NLG reversed the depressive behavior in CUMS mice. The expression level of B4galt1 in CUMS mice was upregulating following the NLG-inhibitor treatment. Similar results haven't been observed in neurons. Information obtained from these experiments showed increasing expression of B4galt1 in microglia following depressive-like behaviors. These findings indicate that NLG in microglia is associated with MDD, and suggest that therapeutically targeting NLG might be an effective strategy for depression. How to modulate the B4galt1 or NLG pathways in microglia efficiently and economically request new technologies. •In CUMS mice, B4galt1 significantly increased in microglia but not in neurons.•Inhibition of N-linked glycosylation could improve depressive-like behavior.•Inhibition of N-linked glycosylation decreased the B4galt1 in microglia.•The expression level of B4galt1 in microglia is positively related to depression.