Imaging the influence of red blood cell docosahexaenoic acid status on the expression of the 18KDa translocator protein in the brain: a [11C]PBR28 PET study in young healthy males

Published:October 01, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.09.005

      ABSTRACT

      OBJECTIVE

      Docosahexaenoic acid (DHA) shows anti-inflammatory/pro-resolution effects in the brain. Higher red blood cell (RBC) DHA in humans is associated with improved cognitive performance and a lower risk for suicide. Here, we hypothesized that binding to the 18KDa translocator protein (TSPO), a proxy for microglia levels, will be higher in individuals with low DHA relative to high DHA levels. We also postulated that higher TSPO would predict poor cognitive performance and impaired stress-resilience.

      METHODS

      RBC DHA screening were performed in 320 healthy males. [11C]PBR28 PET was used to measure binding to TSPO in 38 and 32 males in the lowest and highest RBC DHA quartiles. Volumes of distribution expressed relative to total plasma ligand concentration (VT) was derived using an arterial input function-based kinetic analysis in fourteen brain regions.

      RESULTS

      [11C]PBR28 VT was significantly lower (by 12% and 20% in C/T and C/C rs6971 genotypes) in males with low compared to high RBC DHA. Regional VT was correlated positively and negatively with RBC DHA and serum triglycerides, respectively. No relationships between VT and cognitive performance, or stress-resilience measures were present.

      CONCLUSIONS

      Contrary to our hypothesis, we found lower TSPO binding in low relative to high DHA subjects. It is unclear as to whether low TSPO binding reflects differences in microglia levels and/or triglyceride metabolism in this study. Future studies with specific targets are necessary to confirm DHA’s effect on microglia. These results underscore the need to consider lipid parameters as a factor when interpreting TSPO PET clinical findings.

      Keywords

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