title: Behavioural, metabolic, and endothelial effects of the TNF-α suppressor thalidomide on rats subjected to chronic mild stress and fed an atherogenic diet.
abstract: There is accumulating evidence suggesting that depression is a risk factor for cardiovascular diseases. This study aimed to examine the hypothesis that the proinflammatory cytokine TNF-α would partially explain the link between depression and atherosclerotic endothelial changes. Rats were distributed among 6 groups: (i) control group; (ii) group subjected to chronic mild stress (CMS); (iii) group fed a cholesterol-cholic acid-thiouracil (CCT diet); and (iv) CMS group fed the CCT diet and treated with the vehicle for 8 weeks. The last 2 groups were subjected to CMS-CCT and received thalidomide (THAL) or imipramine (IMIP). Rats were assessed behaviorally (sucrose preference, open field, and forced-swimming tests). TNF-α protein was assessed from the serum, aorta, and liver. Aortic TNF-α gene expression (assessed using RT-PCR), serum lipid profile, and insulin levels were measured. Endothelial function was assessed in isolated aortic rings. The THAL and IMIP groups showed ameliorated CMS-CCT-related behavioral changes. CMS-CCT-induced metabolic and endothelial dysfunctions were improved in the THAL group but were worsened in the IMIP group. RT-PCR showed a significant reduction of aortic TNF-α mRNA expression in the THAL and IMIP treatment groups. These data paralleled the findings for aortic immunohistochemistry. The THAL group, but not the IMIP group, showed improved CMS-CCT-induced changes in the vascular reactivity of the aortic rings. Thus, TNF-α provides a target link between depression, metabolic syndrome, and endothelial dysfunction. This could open a new therapeutic approach to address the comorbidities of depression.
authors.affiliation: a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt.
authors.forename: Basma
authors.initials: B
authors.lastname: Ismail
authors.forename: Sawsan
authors.initials: S
authors.lastname: Aboul-Fotouh
authors.forename: Amal A
authors.initials: AA
authors.lastname: Mansour
authors.forename: Hanan H
authors.initials: HH
authors.lastname: Shehata
authors.forename: Manal I
authors.initials: MI
authors.lastname: Salman
authors.forename: Eman A
authors.initials: EA
authors.lastname: Ibrahim
authors.forename: Olfat A
authors.initials: OA
authors.lastname: Hassan
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abdel-tawab
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003863:Depression / Q000378:metabolism / Q000523:psychology; D004036:Diet, Atherogenic / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013792:Thalidomide; D007099:Imipramine