Bibliographic
Year of Publication:
2008
Contact PI Name:
Rajadas Jayakumar
Primary Reference (PubMED ID):
Funding Source:
Council of Scientific and Industrial Research (CSIR) India
Study Goal and Principal Findings:
Oxidative stress is one of the hypothesized pathogenic mechanisms for neurodegenerative diseases, including Alzheimer's disease (AD); numerous studies suggest that Aβ 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 Aβ35–25 treated, Aβ25–35 injected, and melatonin treated. A single dose of Aβ25–35 (25μg) was administered to mice via intraperitoneal injection. Melatonin (50 mg/kg body weight) was administered intraperitoneally for 3 days to the Aβ25–35 injected mice. Control mice received only physiological saline and Scrambles receives Aβ35–25 single intraperitoneal injection of 25 μg of Aβ35–25. Our study showed that melatonin significantly reduces reactive oxygen species (ROS) production in the astrocytes, lymphocytes and hepatocytes of Aβ 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-κB in liver and neocortex of Aβ 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 Aβ and AD, it can also prevent dopamine turnover induced by Aβ.
Therapeutic Agent
Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Melatonin
Therapeutic Target:
Multi Target
Animal Model
Model Information:
Species:
Mouse
Model Type:
beta Amyloid Peptide Injection
Model Name:
Swiss Albino (beta Amyloid 25-35 Peptide Injection Model)
Strain/Genetic Background:
Swiss
Experimental Design
Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest
Outcomes
Outcome Measured
Outcome Parameters
Biochemical
3,4-dihydroxyphenilacetic Acid (DOPAC)
5-hydroxyindolacetic Acid (5-HIAA)
5-hydroxytryptamine (5-HT)
Dopamine
Homovanillic Acid (HVA)
Noradrenaline/Norepinephrine
Catalase (CAT) Activity
Superoxide Dismutase (SOD) Activity
Glutathione (GSH)
Lipid Peroxidation
Malondialdehyde (MDA)
Reactive Oxygen Species (ROS)
Immunochemistry
Glial Fibrillary Acidic Protein (GFAP)
Nuclear Factor kappa B-RelA (NFkB-p65)
Cell Biology
Intracellular Reactive Oxygen Species