Functional regulation of microglia by vitamin B12 alleviates ischemic stroke-induced neuroinflammation in mice

Yong Ge, Changjun Yang, Mojgan Zadeh, Shane M. Sprague, Yang Ding Lin, Heetanshi Sanjay Jain, Brenden Fitzgerald Determann, William H. Roth, Juan Pablo Palavicini, Jonathan Larochelle, Eduardo Candelario-Jalil, Mansour Mohamadzadeh

Research output: Contribution to journalArticlepeer-review

Abstract

Ischemic stroke is the second leading cause of death and disability worldwide, and efforts to prevent stroke, mitigate secondary neurological damage, and promote neurological recovery remain paramount. Recent findings highlight the critical importance of microbiome-related metabolites, including vitamin B12 (VB12), in alleviating toxic stroke-associated neuroinflammation. Here, we showed that VB12 tonically programmed genes supporting microglial cell division and activation and critically controlled cellular fatty acid metabolism in homeostasis. Intriguingly, VB12 promoted mitochondrial transcriptional and metabolic activities and significantly restricted stroke-associated gene alterations in microglia. Furthermore, VB12 differentially altered the functions of microglial subsets during the acute phase of ischemic stroke, resulting in reduced brain damage and improved neurological function. Pharmacological depletion of microglia before ischemic stroke abolished VB12-mediated neurological improvement. Thus, our preclinical studies highlight the relevance of VB12 in the functional programming of microglia to alleviate neuroinflammation, minimize ischemic injury, and improve host neurological recovery after ischemic stroke.

Original languageEnglish (US)
Article number109480
JournaliScience
Volume27
Issue number4
DOIs
StatePublished - Apr 19 2024

Keywords

  • Immunology
  • Neuroscience
  • Omics
  • Transcriptomics

ASJC Scopus subject areas

  • General

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