Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain

Mai Sakai, Hikaru Takeuchi, Zhiqian Yu, Yoshie Kikuchi, Chiaki Ono, Yuta Takahashi, Fumiaki Ito, Hiroo Matsuoka, Osamu Tanabe, Jun Yasuda, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Tomita

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aim: CX3CR1, a G-protein-coupled receptor, is involved in various inflammatory processes. Two non-synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1-expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia. Methods: Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals. Results: The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators. Conclusion: This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells.

Original languageEnglish
Pages (from-to)409-422
Number of pages14
JournalPsychiatry and Clinical Neurosciences
Volume72
Issue number6
DOIs
Publication statusPublished - 2018 Jun

Keywords

  • CX3CR1
  • arterial blood volume
  • brain
  • magnetic resonance imaging
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain'. Together they form a unique fingerprint.

  • Cite this