Neuroprotective role of neurokinin B (NKB) on beta-amyloid (25-35) induced toxicity in aging rat brain synaptosomes: involvement in oxidative stress and excitotoxicity.
The brain tissue has a large oxidative capacity, but its ability to combat oxidative stress is limited. In aging brain tissue the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stress leading to neurodegeneration associated with excitotoxicity. The aim of the present study was to determine the effect of neuropeptides, neurokinin B (NKB) and amyloid beta protein fragment Abeta (25-35) and neurotransmitters N-methyl D-aspartate (NMDA) and Glutamate on rat brain synaptosomes of different age groups. Aging brain functions were assessed by measuring the activities of superoxide dismutase (Mn-SOD) and monoamine oxidase (MAO) and intrasynaptosomal [Ca(2+)](i )levels in presence of neuropeptides and neurotransmitters. Increase in age decreased the SOD and MAO enzyme activities; Abeta (25-35) addition further had damaging/toxic effects on the enzymes, whereas NKB alone and in combination with amyloid lowered the toxic effects caused by Abeta (25-35) addition, which was concentration (peptide) and age dependent. Oxidative stress and excitotoxicity are major consequences associated with the age, [Ca(2+)](i )was increased with the age and the neuropeptides and neurotransmitters elicited significant modulatory effects on it. Our study elucidates an increased activity of SOD, decreased activity of MAO and restoration of [Ca(2+)](i) levels in the presence of NKB and suggests an antioxidant, neuromodulatory and neuroprotective role of tachykinin peptide NKB against the beta amyloid induced toxicity.
Mantha
Anil K
AK
Molecular and Structural Biophysics Laboratory, School of Life Sciences, Jawaharlal Nehru University, 110067, New Delhi, India.
Moorthy
K
K
Cowsik
Sudha M
SM
Baquer
Najma Z
NZ
D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008995:Monoamine Oxidase / Q000378:metabolism; D016202:N-Methylaspartate / Q000008:administration & dosage; D015287:Neurokinin B / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D018698:Glutamic Acid; D016202:N-Methylaspartate; D015287:Neurokinin B; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase