Brain regional α-[11C]methyl-L-tryptophan trapping, used as an index of 5-HT synthesis, in healthy adults: absence of an age effect
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Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional α-[11C]methyl-L-tryptophan (α-[11C]MTrp) trapping rate constant (K*; μl·g−1·min−1), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis.
Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with α-[11C]MTrp [18 males aged 46.6 ± 22.2 years (range 20–80 years) and 18 females aged 33.0 ± 15.5 years (range 20–80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm.
VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and α-[11C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis.
The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process.
KeywordsPositron emission tomography 5-HT α-MTrp brain trapping Serotonin synthesis Brain morphometry Voxel-based morphometry
The research was supported in part by grants from the NIH, CIHR, and FRSQ. We would like to acknowledge the dedicated technical support from the Radiochemistry-Cyclotron and Positron Emission Tomography Units. M.D. is a Killam Scholar at the Montreal Neurological Institute, McGill University, C.B. holds a Chercheur National Award and M.L. holds a Chercheur Boursier from FRSQ. In addition, we would like to thank S. Milot and S.N. Young for their help and suggestions during this study.
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