Anavex Life Sciences Corp (AVXL)

[georgejjl]

Anavex 2-73 and/or Anavex 3-71 as a potential treatment for diabetic depression

Psychopharmacology (Berl). 2016 Apr;233(7):1269-78. doi: 10.1007/s00213-016-4209-x. Epub 2016 Jan 26.
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 L1,2, Hodrea J1, Hosszu A1, Koszegi S1,3, Zelena D4, Balogh D1,2, Szkibinszkij E1,5, Veres-Szekely A3, Wagner L5, Vannay A3, Szabo AJ2,3, Fekete A6,7.
Author information
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.

http://www.ncbi.nlm.nih.gov/pubmed/26809458

Good luck and GOD bless,

George