title: Melatonin prevents amyloid protofibrillar induced oxidative imbalance and biogenic amine catabolism.
abstract: Oxidative stress is one of the hypothesized pathogenic mechanisms for neurodegenerative diseases, including Alzheimer's disease (AD); numerous studies suggest that Abeta is toxic to neurons by free radical mediated mechanism. A constant feature in AD brain is selective neuronal loss, accompanied by dysfunction of several neurotransmitter systems, such as cholinergic, serotoninergic and noradrenergic systems. In the present study, we studied the neuroprotective role of melatonin against amyloid protofibrils and the toxicity of protofibrils on serotoninergic and noradrenergic systems. Mice were divided into four groups (n=8 each), control, Scrambles Abeta(35-25) treated, Abeta(25-35) injected, and melatonin treated. A single dose of Abeta(25-35) (25 microg) was administered to mice via intraperitoneal injection. Melatonin (50 mg/kg body weight) was administered intraperitoneally for 3 days to the Abeta(25-35) injected mice. Control mice received only physiological saline and Scrambles receives Abeta(35-25) single intraperitoneal injection of 25 microg of Abeta(35-25). Our study showed that melatonin significantly reduces reactive oxygen species (ROS) production in the astrocytes, lymphocytes and hepatocytes of Abeta injected mice by increasing the levels of scavenging enzymes, SOD, catalase and GSH when compared to the untreated group. Immunohistochemistry study reveals that melatonin prevents the activation of GFAP in neocortex and transcription factor NF-kappaB in liver and neocortex of Abeta injected mice. It also prevents the elevation of dopamine depletion and its degradation products. Thus, while melatonin may be a potential therapeutic agent in the prevention of oxidative stress associated with Abeta and AD, it can also prevent dopamine turnover induced by Abeta.
authors.affiliation: Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Chennai, India.
authors.forename: Masilamoni J
authors.initials: MJ
authors.lastname: Gunasingh
authors.forename: Jesudason E
authors.initials: JE
authors.lastname: Philip
authors.forename: Ben S
authors.initials: BS
authors.lastname: Ashok
authors.forename: R
authors.initials: R
authors.lastname: Kirubagaran
authors.forename: W Charles E
authors.initials: WC
authors.lastname: Jebaraj
authors.forename: G Dicky John
authors.initials: GD
authors.lastname: Davis
authors.forename: S
authors.initials: S
authors.lastname: Vignesh
authors.forename: S
authors.initials: S
authors.lastname: Dhandayuthapani
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001679:Biogenic Amines; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C113041:amyloid beta-protein (35-25); D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin