Objective: The aim of the present study was to determine the effects of neuropeptide, neurokinin B (NKB) and amyloid beta fragment Aβ (25-35) on 17β estradiol (E2) treated aging female rat brain of 3 months (young), 12 months (adult) and 24 months (old) age groups.

Background: Alzheimer’s disease (AD) is the most common form of dementia in the elderly. AD is characterized by the presence of amyloid plaques which are formed from deposits of β-amyloid protein (Ab). Accumulation of oligomeric Ab in the brain contributes to neuronal dysfunction and ultimately leads to neurodegeneration. These changes increase during menopausal condition in females when the level of estradiol is decreased

Method: The aged rats (12 and 24 months old) were given subcutaneous injection of E2 (0.1 µg/g body weight) for 30 days. Synaptosomes were incubated with NKB, Aβ (25–35) and NKB+ Aβ (25–35) in a microfuge tubes at 37˚C  for 60 min in a shaking water bath with 0.1, 1 and 5 µM concentration of each of the peptides  in all age groups of control and E2 treated rats. The learning and memory function were assessed by Morris water maze test. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis.

Results: The results obtained in the present work revealed that increased activities of antioxidant enzymes (glutathione reductase, superoxide dismutase and decrease in calcium levels, acetylcholinesterase (AChE) activity, neurolipofusicin accumulation and malondialdehyde (MDA) in presence of NKB and combined NKB and Aβ in vivo E2 treated aging rat brain. An in vitro incubation of E2 treated synaptosomes with Aβ showed toxic effects on all the parameters, while NKB showed stimulating effects and the combined NKB and Aβ showed a partial effects as compared to Aβ (25-35) and NKB alone. Similar results were obtained with the increased antioxidant enzymes levels, improved learning and memory performances, reduced AChE activity and MDA levels, significantly increased PPARγ expression, and alleviated TNF-α, IL-1β, and IL-6 compared with the E2 treated aging rat  hippocampus.

Conclusion: Present study elucidates an antioxidant,anti-aging and neuroprotective role of tachykinin peptide NKB against the beta amyloid induced toxicity in E2 treated female rats.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-and-in-vitro-study-of-17%ce%b2-estradiol-against-amyloid-beta-neurotoxicity-in-synaptosomes-of-aging-female-rats-a-therapeutic-potential-drug-for-alzheimers-disease/