The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats

Lilla Lenart, Judit Hodrea, Adam Hosszu, Sandor Koszegi, Dora Zelena, Dora Balogh, Edgar Szkibinszkij, Apor Veres-Szekely, Laszlo Wagner, Adam Vannay, Attila J. Szabo, Andrea Fekete

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Rationale: 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. Objectives: 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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalPsychopharmacology
DOIs
Publication statusAccepted/In press - Jan 26 2016

Fingerprint

Fluvoxamine
Brain-Derived Neurotrophic Factor
Streptozocin
Depression
Nerve Growth Factors
Brain
Adrenal Glands
sigma-1 receptor
Endoplasmic Reticulum
Thymus Gland

Keywords

  • Brain-derived neurotrophic factor
  • Depression
  • Fluvoxamine
  • Sigma-1 receptor
  • Type 1 diabetes

ASJC Scopus subject areas

  • Pharmacology

Cite this

The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats. / Lenart, Lilla; Hodrea, Judit; Hosszu, Adam; Koszegi, Sandor; Zelena, Dora; Balogh, Dora; Szkibinszkij, Edgar; Veres-Szekely, Apor; Wagner, Laszlo; Vannay, Adam; Szabo, Attila J.; Fekete, Andrea.

In: Psychopharmacology, 26.01.2016, p. 1-10.

Research output: Contribution to journalArticle

Lenart, Lilla ; Hodrea, Judit ; Hosszu, Adam ; Koszegi, Sandor ; Zelena, Dora ; Balogh, Dora ; Szkibinszkij, Edgar ; Veres-Szekely, Apor ; Wagner, Laszlo ; Vannay, Adam ; Szabo, Attila J. ; Fekete, Andrea. / The role of sigma-1 receptor and brain-derived neurotrophic factor in the development of diabetes and comorbid depression in streptozotocin-induced diabetic rats. In: Psychopharmacology. 2016 ; pp. 1-10.
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AU - Zelena, Dora

AU - Balogh, Dora

AU - Szkibinszkij, Edgar

AU - Veres-Szekely, Apor

AU - Wagner, Laszlo

AU - Vannay, Adam

AU - Szabo, Attila J.

AU - Fekete, Andrea

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N2 - Rationale: 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. Objectives: 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.

AB - Rationale: 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. Objectives: 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.

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