guest ::
| Home > Publications database > Serotonergic organiziation of the human brain: A multi-tracer Positron Emission Tomography study of healthy subjects |
| Home > Publications database > Serotonergic organiziation of the human brain: A multi-tracer Positron Emission Tomography study of healthy subjects |
| Abstract | FZJ-2014-00673 |
; ; ; ; ; ; ;
2013
Abstract: Introduction The cerebral cortex has often been subdivided into numerous areas characterized by structural, functional and cytoarchitectonic features while protein-based organizations schemes are lacking [1]. In the current study we propose a new organizational model of the brain based on protein distributions of the serotonergic system including the major inhibitory (5-HT1A and 5-HT1B), the major excitatory (5-HT2A) receptors and the transporter (SERT) of healthy subjects measured with positron emission tomography (PET) and dedicated radioligands. Methods Dynamic PET scans were performed in 95 healthy subjects (age=28.0±6.9 years; 59% males) divided into 4 groups using the selective radioligands [carbonyl-11C]WAY100635 for 5-HT1A, [18F]altanserin for 5-HT2A, [11C]P943 for 5-HT1B and [11C]DASB for SERT. Similarities between receptor distribution patterns were analyzed by means of a hierarchical cluster analysis using Euclidean distances in combination with the Ward-linkage method as implemented in R2.15.2. All values were z-transformed across areas prior to analysis in order to establish equal weight between the protein bindings. Results Hierarchical cluster analysis of group-average binding potential values revealed two main protein-distinct clusters. The first exclusively comprised subcortical areas such as the raphe nuclei, thalamus, pallidum, caudate nucleus, putamen, midbrain, and striatum, whereas in the second the remaining cortical areas were aggregated. The two main subclusters from the cortical areas partly follow lobular definitions. The first predominantly comprises frontal, parietal, occipital, and cingulate regions of interest (ROIs) while no marked distinctions are found in further subclusters. The second mainly contains temporal ROIs, but also some frontal ROIs and the hippocampal-amygdala ROIs although with stronger Euclidean distance than cortical ROIs. Discussion Applying a data-driven approach we identified brain regions of similar features within the serotonergic system. Interestingly, spatially distant ROIs such as the subcortical areas were identified with close molecular similarity in contrast to cortical ROIs as given by the large Euclidean distance between these two clusters. The two clusters found were in accordance with the familiar classification of cortical und subcortical ROIs. In the lower clusters stringent lobular definition vanishes. This result reflects an explicit hierarchical organization of the serotonergic system and emphasizes functions and interactions of the binding proteins beyond topologies. Acknowledgements: This research was partly supported by grants from the Austrian National Bank (OeNB 13214 to R.L. and OeNB 13675 to M.M.), the Austrian Science Fund and by an unrestricted investigator-initiated research grant from H. Lundbeck A/S to S.K. References Savli M, Bauer A, Mitterhauser M, Ding YS, Hahn A, Kroll T, Neumeister A, Haeusler D, Ungersboeck J, Henry S, Isfahani SA, Rattay F, Wadsak W, Kasper S, Lanzenberger R: Normative database of the serotonergic system in healthy subjects using multitracer PET. NeuroImage, 2012; 63: 447–459.
|
The record appears in these collections: |