title: Mechanism of the beneficial effect of melatonin in experimental Parkinson's disease.
abstract: This study aimed to elucidate locomotor activity changes in 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) and investigate the possible beneficial effects of melatonin on altered levels of locomotor activity, cyclooxygenase (COX), prostaglandin E2 (PGE2), nuclear factor kappa-B (NF-κB), nitrate/nitrite and apoptosis. Male Wistar rats were divided into five groups: vehicle (V), melatonin-treated (M), 6-OHDA-injected (6-OHDA), 6-OHDA-injected + melatonin-treated (6-OHDA-Mel) and melatonin treated + 6-OHDA-injected (Mel-6-OHDA). Melatonin was administered intraperitoneally at a dose of 10 mg/kg/day for 30 days in M and Mel-6-OHDA groups, for 7 days in 6-OHDA-Mel group. Experimental PD was created stereotactically via unilateral infusion of 6-OHDA into the medial forebrain bundle (MFB). The 6-OHDA-Mel group started receiving melatonin when experimental PD was created and treatment was continued for 7 days (post-treatment). In the Mel-6-OHDA group, experimental PD was created on the 23rd day of melatonin treatment and continued for the remaining 7 days (pre- and post-treatment). Locomotor activity performance decreased in 6-OHDA group compared with vehicle; however melatonin treatment did not improve this impairment. Nuclear factor kappa Bp65 and Bcl-2 levels were significantly decreased while COX, PGE2 and caspase-3 activity were significantly increased in 6-OHDA group. Melatonin treatment significantly decreased COX, PGE2 and caspase-3 activity, increased Bcl-2 and had no effect on NF-κB levels in experimental PD. 6-Hydroxydopamine injection caused an obvious reduction in TH positive dopaminergic neuron viability as determined by immunohistochemistry. Melatonin supplementation decreased dopaminergic neuron death in 6-OHDA-Mel and Mel-6-OHDA groups compared with 6-OHDA group. Melatonin also protected against 6-OHDA-induced apoptosis, as identified by increment in Bcl-2 levels in dopaminergic neurons. The protective effect of melatonin was more prominent for most parameter following 30 days treatment (pre- and post-) than 7 days post-treatment. In summary, melatonin treatment decreased dopaminergic neuron death in experimental PD model by increasing Bcl-2 protein level and decreasing caspase-3 activity.
authors.affiliation: Faculty of Medicine, Department of Anatomy, Akdeniz University, Antalya, Turkey.
authors.forename: Fatos Belgin
authors.initials: FB
authors.lastname: Yildirim
authors.affiliation: Faculty of Medicine, Department of Physiology, Akdeniz University, Antalya, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Ozsoy
authors.affiliation: Faculty of Medicine, Department of Histology and Embryology, Akdeniz University, Antalya, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Tanriover
authors.affiliation: Faculty of Medicine, Department of Anatomy, Akdeniz University, Antalya, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Kaya
authors.affiliation: Faculty of Medicine, Department of Anatomy, Akdeniz University, Antalya, Turkey.
authors.forename: Eren
authors.initials: E
authors.lastname: Ogut
authors.affiliation: Faculty of Medicine, Department of Physiology, Akdeniz University, Antalya, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Gemici
authors.affiliation: Faculty of Medicine, Department of Histology and Embryology, Akdeniz University, Antalya, Turkey.
authors.forename: Sayra
authors.initials: S
authors.lastname: Dilmac
authors.affiliation: Faculty of Medicine, Department of Physiology, Akdeniz University, Antalya, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Ozkan
authors.affiliation: Faculty of Medicine, Department of Physiology, Akdeniz University, Antalya, Turkey. Electronic address: ayagar@akdeniz.edu.tr.
authors.forename: Aysel
authors.initials: A
authors.lastname: Agar
authors.affiliation: Faculty of Medicine, Department of Biochemistry, Akdeniz University, Antalya, Turkey.
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D059290:Dopaminergic Neurons / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016627:Oxidopamine; D008550:Melatonin
keywords: 6-Hydroxydopamine; Apoptosis; Cyclooxygenase; Melatonin; Nuclear factor kappa B; Prostaglandin E2