Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? : A 1H magnetic resonance spectroscopy study at 7 tesla

Anna Lind, Carl-Johan Boraxbekk, Esben Thade Petersen, Olaf Bjarne Paulson, Ove Andersen, Hartwig Roman Siebner, Anouk Marsman*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) were measured on the same day as 1H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing.
Original languageEnglish
JournalJournal of Neurochemistry
Volume159
Issue number1
Pages (from-to)185-196
ISSN0022-3042
DOIs
Publication statusPublished - 2021

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