title: Increased cortical expression of the zinc transporter SLC39A12 suggests a breakdown in zinc cellular homeostasis as part of the pathophysiology of schizophrenia.
abstract: Our expression microarray studies showed messenger RNA (mRNA) for solute carrier family 39 (zinc transporter), member 12 (SLC39A12) was higher in dorsolateral prefrontal cortex from subjects with schizophrenia (Sz) in comparison with controls. To better understand the significance of these data we ascertained whether SLC39A12 mRNA was altered in a number of cortical regions (Brodmann's area (BA) 8, 9, 44) from subjects with Sz, in BA 9 from subjects with mood disorders and in rats treated with antipsychotic drugs. In addition, we determined whether inducing the expression of SLC39A12 resulted in an increased cellular zinc uptake. SLC39A12 variant 1 and 2 mRNA was measured using quantitative PCR. Zinc uptake was measured in CHO cells transfected with human SLC39A12 variant 1 and 2. In Sz, compared with controls, SLC39A12 variant 1 and 2 mRNA was higher in all cortical regions studied. The were no differences in levels of mRNA for either variant of SLC39A12 in BA 9 from subjects with mood disorders and levels of mRNA for Slc39a12 was not different in the cortex of rats treated with antipsychotic drugs. Finally, expressing both variants in CHO-K1 cells was associated with an increase in radioactive zinc uptake. As increased levels of murine Slc39a12 mRNA has been shown to correlate with increasing cellular zinc uptake, our data would be consistent with the possibility of a dysregulated zinc homeostasis in the cortex of subjects with schizophrenia due to altered expression of SLC39A12.
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychaitry, University of Melbourne, Melbourne, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Madhara
authors.initials: M
authors.lastname: Udawela
authors.affiliation: Oxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health , Parkville, VIC, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Greenough
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Neo
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health , Parkville, VIC, Australia.
authors.forename: Myoung
authors.initials: M
authors.lastname: Suk Seo
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychaitry, University of Melbourne, Melbourne, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Tammie T
authors.initials: TT
authors.lastname: Money
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Aradhana
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: CRC for Mental Health, Carlton South, VIC, Australia; Oxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
authors.forename: Ashley I
authors.identifier: 0000-0001-8259-9069
authors.initials: AI
authors.lastname: Bush
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychaitry, University of Melbourne, Melbourne, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Everall
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute , La Jolla, CA, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thomas
authors.affiliation: The Molecular Psychiatry Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychaitry, University of Melbourne, Melbourne, VIC, Australia; CRC for Mental Health, Carlton South, VIC, Australia.
authors.forename: Brian
authors.identifier: 0000-0001-7773-4473
authors.initials: B
authors.lastname: Dean