A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

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  • Additional Information
    • Source:
      Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : Society for Neuroscience
      Original Publication: [Baltimore, Md.] : The Society, c1981-
    • Subject Terms:
      Atlases as Topic* ; Brain Chemistry*; Brain/*anatomy & histology ; Receptors, Serotonin/*metabolism ; Serotonin/*metabolism; Adult ; Autoradiography ; Brain/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neuroimaging ; Positron-Emission Tomography ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Young Adult
    • Abstract:
      The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain.
      Significance Statement: We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders.
      (Copyright © 2017 the authors 0270-6474/17/370120-09$15.00/0.)
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    • Grant Information:
      R21 EB018964 United States EB NIBIB NIH HHS; S10 RR023043 United States RR NCRR NIH HHS
    • Contributed Indexing:
      Keywords: 5-HT; MRI; PET; atlas; autoradiography; mRNA
    • Accession Number:
      0 (RNA, Messenger)
      0 (Receptors, Serotonin)
      0 (Serotonin Plasma Membrane Transport Proteins)
      333DO1RDJY (Serotonin)
    • Publication Date:
      Date Created: 20170106 Date Completed: 20170724 Latest Revision: 20190910
    • Publication Date:
      20240829
    • Accession Number:
      PMC5214625
    • Accession Number:
      10.1523/JNEUROSCI.2830-16.2016
    • Accession Number:
      28053035