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European Journal of Nuclear Medicine and Molecular Imaging

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15.08.2023 | Original Article

Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain

verfasst von: Yasuharu Yamamoto, Keisuke Takahata, Manabu Kubota, Hiroyoshi Takeuchi, Sho Moriguchi, Takeshi Sasaki, Chie Seki, Hironobu Endo, Kiwamu Matsuoka, Kenji Tagai, Yasuyuki Kimura, Shin Kurose, Masaru Mimura, Kazunori Kawamura, Ming-Rong Zhang, Makoto Higuchi

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2023

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Abstract

Purpose

The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters. This discrepancy may be due to differences in regulation after transcription between presynaptic and postsynaptic proteins, which have not been studied in the dopaminergic system. Here, we focused on dopamine D1 and D2/D3 receptors and dopamine transporters and investigated their region-wise relationship between mRNA expression and protein distribution.

Methods

We examined the region-wise correlation between regional binding potentials of the target region relative to that of non-displaceable tissue (BP_ND) values of ¹¹C-SCH-23390 and mRNA expression levels of dopamine D1 receptors (D1R); regional BP_ND values of ¹¹C-FLB-457 and mRNA expression levels of dopamine D2/D3 receptors (D2/D3R); and regional total distribution volume (V_T) values of ¹⁸F-FE-PE2I and mRNA expression levels of dopamine transporters (DAT) using Spearman’s rank correlation.

Results

We found significant positive correlations between regional BP_ND values of ¹¹C-SCH-23390 and the mRNA expression levels of D1R (r = 0.769, p = 0.0021). Similar to D1R, regional BP_ND values of ¹¹C-FLB-457 positively correlated with the mRNA expression levels of D2R (r = 0.809, p = 0.0151) but not with those of D3R (r = 0.413, p = 0.3095). In contrast to D1R and D2R, no significant correlation between V_T values of ¹⁸F-FE-PE2I and mRNA expression levels of DAT was observed (r = -0.5934, p = 0.140).

Conclusion

We found a region-wise correlation between the mRNA expression levels of dopamine D1 and D2 receptors and their respective protein distributions. However, we found no region-wise correlation between the mRNA expression levels of dopamine transporters and their protein distributions, indicating different regulatory mechanisms for the localization of pre- and postsynaptic proteins. These results provide a broader understanding of the application of the transcriptome atlas to neuroimaging studies of the dopaminergic nervous system.

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Titel: Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain
verfasst von: Yasuharu Yamamoto
Keisuke Takahata
Manabu Kubota
Hiroyoshi Takeuchi
Sho Moriguchi
Takeshi Sasaki
Chie Seki
Hironobu Endo
Kiwamu Matsuoka
Kenji Tagai
Yasuyuki Kimura
Shin Kurose
Masaru Mimura
Kazunori Kawamura
Ming-Rong Zhang
Makoto Higuchi
Publikationsdatum: 15.08.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2023
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06390-2

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Association of protein distribution and gene expression revealed by positron emission tomography and postmortem gene expression in the dopaminergic system of the human brain

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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