An immunohistochemical study of the effects of pentoxyphylline 'PENT', and the nNOS inhibitor 7 – nitroindazole '7 – IND' on TNF-α' and Indoleamine 2, 3 –dioxygenase (IDO) enzyme in the hippocampus of chronic mild stress ‘CMS'-exposed rats: A comparison with the effects of imipramine 'IMIP'
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1
National Research Centre, Department of Pharmacology, Egypt
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2
Faculty of Medicine, Ain Shams University, Department of Pathology, Egypt
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3
Faculty of Medicine, Ain Shams University, Department of Pharmacology, Egypt
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4
Ain Shams University, Department of Biochemistry, Faculty of Medicine, Egypt
Background: Evidence suggests a role of TNF-α in the dysregulation of IDO enzyme, and hence 5-HT availability. This is hypothesized as one of the processes underlying the neurobiology of depression. The present study aims at using pharmacological tools to probe the link of this dysregulation with the neuronal nitric oxide synthase 'nNOS' enzyme in CMS (an animal model of depression). Methods: Male Wistar rats were divided into 5 groups; 2 (control and CMS-exposed for 6 weeks) and another 3 groups exposed to CMS and administered pentoxyphylline ‘PENT’ 50 mg/kg/day i.p., 7-nitroindazole ‘7-IND 40 mg/kg/day s.c. or imipramine ‘IMIP’ 20 mg/kg/day i.p, for the last three CMS weeks. Rats were assessed for sucrose preference and forced swimming immobilization. Immunohistochemical study for IDO enzyme and TNF-α were done in the hippocampus, and midbrain. Serum TNF-α was measured in all groups. Results: PENT, 7-IND and IMIP exposed rats showed amelioration of CMS-related behavioural responses. Serum TNF-α in the CMS, PENT and 7-IND groups was [26.20±1.83, 18.54±0.85 and 19.16±1.54 pg/ml, respectively. p < 0.05]. Immunohistochemistry revealed strong positive TNF-α in the hippocampus and midbrain, and IDO staining in midbrain of the CMS group. In both areas, TNF-α staining was mild positive in PENT and 7-IND, moderate in IMIP treated groups. IDO staining was negative in the midbrain of all drug-treated groups. Conclusion: nNOS’ and TNF-α may play a role in modulating IDO enzyme activity in the CMS exposed rats and raise the possibility for alternative pharmacological approaches to understand the neurobiology of depression.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Neurobiology of pain and depression
Citation:
Amin
B,
Ibrahim
EA,
Aboul-Fotouh
SA,
Shehata
HH,
Yassin
N and
Abdel-Tawab
AM
(2009). An immunohistochemical study of the effects of pentoxyphylline 'PENT', and the nNOS inhibitor 7 – nitroindazole '7 – IND' on TNF-α' and Indoleamine 2, 3 –dioxygenase (IDO) enzyme in the hippocampus of chronic mild stress ‘CMS'-exposed rats: A comparison with the effects of imipramine 'IMIP'.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.124
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Received:
24 Nov 2009;
Published Online:
24 Nov 2009.
*
Correspondence:
Ahmed M Abdel-Tawab, Faculty of Medicine, Ain Shams University, Department of Pharmacology, Cairo, Egypt, amtawab@yahoo.com