title: Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor.
abstract: BACKGROUND
  Data indicated that zinc deficiency may contribute to the development of depression; however changes induced by zinc deficiency are not fully described.
  
  
  OBJECTIVE
  In the present paper we tested whether the dietary zinc restriction in rats causes alterations in N-methyl-D-aspartate receptor (NMDAR) subunits in brain regions that are relevant to depression.
  
  
  METHODS
  Male Sprague Dawley rats were fed a zinc adequate diet (ZnA, 50 mg Zn/kg) or a zinc deficient diet (ZnD, 3 mg Zn/kg) for 4 or 6weeks. Then, the behavior of the rats was examined in the forced swim test, sucrose intake test and social interaction test. Western blot assays were used to study the alterations in NMDAR subunits GluN2A and GluN2B and proteins associated with NMDAR signaling in the hippocampus (Hp) and prefrontal cortex (PFC).
  
  
  RESULTS
  Following 4 or 6 weeks of zinc restriction, behavioral despair, anhedonia and a reduction of social behavior occurred in rats with concomitant increased expression of GluN2A and GluN2B and decreased expression of the PSD-95, p-CREB and BDNF protein levels in the Hp. The up-regulation of GluN2A protein was also found in the PFC, but only after prolonged (6 weeks) zinc deprivation.
  
  
  CONCLUSIONS
  The procedure of zinc restriction in rats causes behavioral changes that share some similarities to the pathophysiology of depression. Obtained data indicated that depressive-like behavior induced by zinc deficiency is associated with the changes in NMDAR signaling pathway.
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Doboszewska
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sowa-Kućma
authors.affiliation: Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Młyniec
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Pochwat
authors.affiliation: Department of Behavioral Neuroscience & Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Hołuj
authors.affiliation: Faculty of Physics and Applied Computer Sciences, AGH University of Science and Technology, Mickiewicza 30, PL 30-059 Kraków, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Ostachowicz
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland; Faculty of Health Sciences, Jagiellonian University Medical College, Michałowskiego 20, PL 31-126 Kraków, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland; Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.affiliation: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. Electronic address: szewczyk@if-pan.krakow.pl.
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Szewczyk
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D005518:Food Preferences / Q000523:psychology; D007398:Interpersonal Relations; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*; D015032:Zinc / Q000097:blood / Q000172:deficiency*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D013395:Sucrose; D015032:Zinc; C501449:Dlg4 protein, rat; C121001:NR2B NMDA receptor
keywords: Forced swim test; NMDA receptor; Social interaction test; Sucrose intake test; Zinc deficiency