Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1H magnetic resonance spectroscopy study at 7 tesla
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Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1H-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 tumour 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. (Figure presented.).
Originalsprog | Engelsk |
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Tidsskrift | Journal of Neurochemistry |
Vol/bind | 159 |
Udgave nummer | 1 |
Sider (fra-til) | 185-196 |
ISSN | 0022-3042 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
This work was supported by The Danish Agency for Science, Technology and Innovation grant no. 0601‐01370B, Lundbeck Foundation grant no. R118‐A11719, and The John and Birthe Meyer Foundation. Hartwig R. Siebner holds a 5‐year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (grant no. R186‐2015‐2138).
Publisher Copyright:
© 2021 International Society for Neurochemistry
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