• Sawsan Aboul-fotouh 1-Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. 2-Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
  • Doaa Mohamed Hassan Central Laboratories, Ministry of Health, Cairo, Egypt.
  • Mohamed Zaki Eldeen Habib Department of Pharmacology, Faculty of Medicine, Ain shams University
  • Ahmed Ibrahim Amin Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
  • Samar K. Kassim Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
  • Amr Saad Mohamed Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.



 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.

Keywords: Fluoxetine, Imipramine, Chronic restraint stress, Depression, Diabetes mellitus, Toll-like receptor-4, Brain-derived neurotrophic factor.


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How to Cite
Aboul-fotouh, S., D. M. Hassan, M. Z. E. Habib, A. I. Amin, S. K. Kassim, and A. S. Mohamed. “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”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 1, Jan. 2018, pp. 271-7, doi:10.22159/ajpcr.2018.v11i1.21593.
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