title: Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.
abstract: Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein.
  
  
  
  Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method.
  
  
  
  There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD-95 and 5-HT1A in MDD.
  
  
  
  Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland; Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rafalo-Ulinska
authors.affiliation: Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Piotrowska
authors.affiliation: Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Kryczyk
authors.affiliation: Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Opoka
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sowa-Kucma
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland; Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Misztak
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; Department of Psychiatry, Case Western Reserve University, 10524 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.affiliation: Department of Affective Disorders, Jagiellonian University Medical College, Kopernika 21a, 31-501 Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Datka
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland; Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. Electronic address: szewczyk@if-pan.krakow.pl.
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Szewczyk
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D002352:Carrier Proteins / Q000378:metabolism*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D000076122:Disks Large Homolog 4 Protein; D055664:Electrochemical Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013405:Suicide / Q000523:psychology*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D044282:Receptor, Serotonin, 5-HT1A; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C501444:DLG4 protein, human; C017800:zinc-binding protein
keywords: 5-HT1A; Glutamate receptors; Major depressive disorder; Suicide; Zinc; Zn transporters