Regional distribution of serotonin transporter protein in postmortem human brain: is the cerebellum a SERT-free brain region?
BACKGROUND
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
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.


CONCLUSIONS
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.
Kish
Stephen J
SJ
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada M5T 1R8. Stephen_Kish@CAMH.net
Furukawa
Yoshiaki
Y
Chang
Li-Jan
LJ
Tong
Junchao
J
Ginovart
Nathalie
N
Wilson
Alan
A
Houle
Sylvain
S
Meyer
Jeffrey H
JH
D015153:Blotting, Western / Q000379:methods*; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D002531:Cerebellum / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012016:Reference Values; D050486:Serotonin Plasma Membrane Transport Proteins; D014018:Tissue Distribution
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins