BIOCHEMICAL STUDIES OF HIPPOCAMPAL GENE EXPRESSION OF BRAIN-DERIVED NEUROTROPIC FACTOR AND TOLL-LIKE RECEPTOR-4 IN DIABETIC RATS EXPOSED TO CHRONIC STRESS: EFFECTS OF ANTIDEPRESSANT DRUGS

• Published in: Asian journal of pharmaceutical and clinical research Vol. 11; no. 1; p. 271
• Main Authors: Aboul-fotouh, Sawsan, Hassan, Doaa Mohamed, Habib, Mohamed Zaki Eldeen, Amin, Ahmed Ibrahim, Kassim, Samar K., Mohamed, Amr Saad
• Format: Journal Article
• Language: English
• Published: 01.01.2018
• ISSN: 0974-2441; 0974-2441
• DOI: 10.22159/ajpcr.2017.v11i1.21593

  Objective: Depression and diabetes are closely associated in a reciprocal manner, leading to significant morbidity and mortality with an evidence of a pro-inflammatory state underlying pathophysiology of both diseases. Unfortunately, little information is available about the effects of antidepressant drugs on hippocampal brain-derived neurotrophic factor (BDNF) and toll-like receptor-4 (TLR-4) expression in diabetes.Methods: We investigated the effect of chronic administration of fluoxetine (FLU) and imipramine (IMIP) on behavioral, metabolic, and inflammatory abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP. Diabetic and non-diabetic rats exposed to CRS showed a significant increase in hippocampal expression of TLR-4 and pro-inflammatory cytokines alongside a decrease in BDNF expression. FLU and IMIP ameliorated these inflammatory abnormalities.Conclusion: Diabetes mellitus (DM) and chronic stress induced a depressive-like behavior associated with an increase in hippocampal expression of TLR-4, tumor necrosis factor-α, and interleukin-1ß with a significant correlation to decreased BDNF expression. FLU and IMIP showed comparable effects regards the improvement of depressive and inflammatory abnormalities associated with DM.