title: Fluvoxamine maleate normalizes striatal neuronal inflammatory cytokine activity in a Parkinsonian rat model associated with depression.
abstract: Cytokine dysfunction is associated with both depression and Parkinson's disease (PD) pathophysiology. Inflammatory cytokines in neural and behavioral processes are involved in the production and/or maintenance of depression in PD. In this study we looked at how Fluvoxamine treatment regulates depressive-like signs, motor impairments and the expression of IL-1β, IL-6, TNF-α, TGF-β and IL-10 cytokines in the striatum of a stressed Parkinsonian rat model. Early maternal separation was used to model stress and depressive-like signs in rats. Maternally separated adult rats were treated with Fluvoxamine for 30days prior to 6-hydroxydopamine (6-OHDA) lesion. The sucrose preference test (SPT) and the limb-use asymmetry test (cylinder test) were used to evaluate anhedonia and motor impairments respectively. Lipid peroxidation and cytokine expression were measured in striatal tissue using ELISA and real-time PCR techniques respectively. Our results show that maternal separation resulted in anhedonia and exacerbated 6-OHDA lesion but Fluvoxamine treatment attenuated these effects. Lipid peroxidation, mRNA levels of IL-1β, IL-6 and TNF-α were down-regulated while IL-10 and TGF-β levels were up-regulated in the lesioned striatum of Fluvoxamine treated rats. This study shows that early treatment with Fluvoxamine may attenuate inflammation on injured striatal neurons by favoring anti-inflammatory cytokine expression while decreasing pro-inflammatory cytokine release in the brain. This suggests a role of Fluvoxamine as a potential therapeutic intervention targeting neuronal inflammation associated with PD.
authors: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
authors: Ernest
authors: E
authors: Dallé
authors: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
authors: Willie M U
authors: WM
authors: Daniels
authors: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa. Electronic address: mabandlam@ukzn.ac.za.
authors: Musa V
authors: MV
authors: Mabandla
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D016666:Fluvoxamine / Q000627:therapeutic use*; D007839:Functional Laterality; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications*; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D014151:Anti-Anxiety Agents; D016207:Cytokines; D012333:RNA, Messenger; D013395:Sucrose; D016627:Oxidopamine; D016666:Fluvoxamine; D003891:Desipramine
keywords: Depression; Fluvoxamine maleate; Inflammatory cytokines; Parkinson’s disease; Striatum