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Neuroprotective Role of Neurokinin B (NKB) on β-amyloid (25–35) Induced Toxicity in Aging Rat Brain Synaptosomes: Involvement in Oxidative Stress and Excitotoxicity

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Abstract

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 Aβ (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 [Ca2+]i levels in presence of neuropeptides and neurotransmitters. Increase in age decreased the SOD and MAO enzyme activities; Aβ (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 Aβ (25–35) addition, which was concentration (peptide) and age dependent. Oxidative stress and excitotoxicity are major consequences associated with the age, [Ca2+]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 [Ca2+]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.

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Abbreviations

AD:

Alzheimer’s disease

Aβ (25–35):

amyloid beta protein fragment (25–35)

[Ca2+]i:

intrasynaptosomal calcium concentration

CNS:

central nervous system

5-HT:

5-hydroxytryptamine

MAO:

monoamine oxidase

NBM:

nucleus basalis magnocellularis

NKA:

neurokinin A

NKB:

neurokinin B

NK1, 2 and 3:

neurokinin receptor 1, 2 and 3 respectively

NMDA:

N-methyl d-aspartate

PD:

Parkinson’s disease

ROS:

reactive oxygen species

SOD:

superoxide dismutase

SP:

substance P

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Mantha, A.K., Moorthy, K., Cowsik, S.M. et al. Neuroprotective Role of Neurokinin B (NKB) on β-amyloid (25–35) Induced Toxicity in Aging Rat Brain Synaptosomes: Involvement in Oxidative Stress and Excitotoxicity. Biogerontology 7, 1–17 (2006). https://doi.org/10.1007/s10522-005-6043-0

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