title: The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression.
  
  
  OBJECTIVE
  We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway.
  
  
  METHODS
  We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions.
  
  
  RESULTS
  In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU.
  
  
  CONCLUSIONS
  We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Bókay János u. 53-54, 1083, Budapest, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Lenart
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Hodrea
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Hosszu
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|MTA-SE Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Koszegi
authors.affiliation: Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Zelena
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|1st Department of Pediatrics, Semmelweis University, Bókay János u. 53-54, 1083, Budapest, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Balogh
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.|Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Edgar
authors.initials: E
authors.lastname: Szkibinszkij
authors.affiliation: MTA-SE Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Apor
authors.initials: A
authors.lastname: Veres-Szekely
authors.affiliation: Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Wagner
authors.affiliation: MTA-SE Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Vannay
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Bókay János u. 53-54, 1083, Budapest, Hungary.|MTA-SE Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabo
authors.affiliation: MTA-SE "Lendület" Diabetes Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary. fekete.andrea@med.semmelweis-univ.hu.|1st Department of Pediatrics, Semmelweis University, Bókay János u. 53-54, 1083, Budapest, Hungary. fekete.andrea@med.semmelweis-univ.hu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003863:Depression / Q000150:complications / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D016666:Fluvoxamine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D000097605:Sigma-1 Receptor
chemical_list: D000840:Anisoles; D019208:Brain-Derived Neurotrophic Factor; D016666:Fluvoxamine; D009292:Narcotic Antagonists; D011437:Propylamines; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D000097605:Sigma-1 Receptor; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
keywords: Brain-derived neurotrophic factor; Depression; Fluvoxamine; Sigma-1 receptor; Type 1 diabetes
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