Anti-inflammatory effect of melatonin on A beta vaccination in mice.
A beta vaccination as a therapeutic intervention of Alzheimer's has many challenges, key among them is the regulation of inflammatory processes concomitant with excessive generation of free radicals seen during such interventions. Here we report the beneficial effects of melatonin on inflammation associated with A beta vaccination in the central and peripheral nervous system of mice. Mice were divided into three groups (n=8 in each): control, inflammation (IA), and melatonin-treated (IAM). The brain, liver, and spleen samples were collected after 5 days for quantitative assessment of plasma lipid peroxides (LPO), an oxidative stress marker, and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (Gpx). IA group mice have shown the elevated concentration of LPO significantly while there was a reduction at antioxidant enzyme levels. In addition, a significant (P<0.05) reduction in neurotransmitters like dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) was also observed in the IA group mice. Nevertheless, their metabolites, such as homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly (P<0.05) as compared to control. Samples were further evaluated at microscopic level to examine the neuropathological changes by immunohistochemical methods. Melatonin treatment effectively reversed these above changes and normalized the LPO and antioxidant enzyme levels (P<0.05). Furthermore, melatonin salvaged the brain cells from inflammation. Our Immunohistochemical findings in the samples of melatonin-treated animals (IAM group) indicated diminished expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (Nf kappa B) than those observed in the IA group samples. Our results suggest that administration of melatonin protects inflammation associated with A beta vaccination, through its direct and indirect actions and it can be an effective adjuvant in the development of vaccination in immunotherapy for Alzheimer's disease (AD).
Jesudason
E Philip
EP
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, 600 020, Tamilnadu, India.
Baben
B'Joe
B
Ashok
Ben S
BS
Masilamoni
J Gunasingh
JG
Kirubagaran
R
R
Jebaraj
W Charles E
WC
Jayakumar
R
R
D000251:Adenosine Triphosphatases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014611:Vaccination / Q000009:adverse effects*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D000251:Adenosine Triphosphatases; D008550:Melatonin