Regional distribution of serotonin transporter protein in postmortem human brain
Abstract
Introduction The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a "SERT-free" reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed.Objective and methods To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects.Results Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values.Conclusion Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.
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In normal post-mortem human cerebellum, SERT concentration is relatively low compared to other brain regions except white matter, allowing its use as a reference region in binding studies.
“In normal post-mortem human cerebellum, there is a relatively low concentration of 5-HT transporters (SERT) compared to other brain regions except in the white matter and can be used as a reference region in binding studies looking at other brain regions with higher binding densities [184].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [184]
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- Authors
- Kish, S. J., Furukawa, Y., Chang, L.-J., Tong, J., Ginovart, N., Wilson, A., Houle, S., & Meyer, J. H.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Kish, Stephen J.
- ORCID
- Venue
- Nuclear Medicine and Biology
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 32
- Issue
- 2
- Pages
- 123-128
- ISSN
- 0969-8051 (ISSN-L)
- OpenAlex
- W55536439
- Cited by
- 179
- References
- 33
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 13 · 2013: 12 · 2012: 11
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nuclear Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute on Drug Abuse (DA 7182, R01DA007182)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- serotonin transporter, postmortem brain, cerebellar cortex, white matter, reference region, non-specific binding, major depressive disorder, ecstasy, serotonergic neurons
- MeSH terms
- Brain, Cadaver, Cerebellum, Humans, Membrane Glycoproteins, Middle Aged, Nerve Tissue Proteins, Neurons, Reference Values, Tissue Distribution, Blotting, Western, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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