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


Sawsan Aboul-fotouh, Doaa Mohamed Hassan, Mohamed Zaki Eldeen Habib, Ahmed Ibrahim Amin, Samar K. Kassim, Amr Saad Mohamed

Abstract


 

 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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About this article

Title

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

Keywords

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

DOI

10.22159/ajpcr.2018.v11i1.21593

Date

01-01-2018

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 11 Issue 1 January 2018 Page: 271-277

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

35 Views | 67 Downloads

Authors & Affiliations

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.
Egypt

Doaa Mohamed Hassan
Central Laboratories, Ministry of Health, Cairo, Egypt.
Egypt

Mohamed Zaki Eldeen Habib
Department of Pharmacology, Faculty of Medicine, Ain shams University
Egypt

Ahmed Ibrahim Amin
Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
Egypt

Samar K. Kassim
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Egypt

Amr Saad Mohamed
Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
Egypt


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