The protective role of DL-alpha-lipoic acid in biogenic amines catabolism triggered by Abeta amyloid vaccination in mice.
The major pathological consequence of Alzheimer disease (AD) is accumulation of beta-amyloid (Abeta) peptide fibrillar plaque in the brain and subsequent inflammatory reaction associated with the surrounding cells due to the presence of these aggregates. Inflammation is the major complication associated with Abeta peptide vaccination. Abeta peptide activated T-helper cells are shown to enhance the existing-inflammatory conditions in the brain and other organs of AD patients. Hence systematic studies on potential approaches that will prevent inflammation during the vaccination are highly desired. DL-alpha-lipoic acid (LA), an antioxidant with known function as cofactor in mitochondrial dehydrogenase reactions, will be a good candidate to annul the oxidative damage due to vaccination triggered inflammation. For the first time, levels of principal neurotransmitters and their major metabolites in hippocampus and neocortex regions of brain are quantified to find out the level of inflammation. We have used high performance liquid chromatography with electro chemical detection (HPLC-EC) for monitoring neurotransmitter levels. We have shown a significant (p<0.05) reduction of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the systemic inflammation induced (SI), vaccinated (VA) and inflammation induced vaccinated (IV) mice. Nevertheless their metabolites such as 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) are significantly (p<0.05) increased when compared with control. Interestingly, antioxidant LA treated mice with systemic inflammation (IL), vaccinated (VL) and inflammation induced vaccinated (IVL) mice exhibited enhanced level of 5-HT, DA and NE and the concentration of 5-HIAA and HVA gradually returned to normal. These results suggest a possible new way for monitoring and modifying the inflammation and thereby preventing Abeta vaccination mediated tissue damage.
Jesudason
E Philip
EP
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Masilamoni
J Gunasingh
JG
Kirubagaran
R
R
Davis
G Dicky John
GD
Jayakumar
R
R
D016229:Amyloid beta-Peptides / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D012835:Silver Nitrate; D008063:Thioctic Acid / Q000627:therapeutic use*; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001679:Biogenic Amines; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D008063:Thioctic Acid; D012835:Silver Nitrate