P3‐324: Beta‐amyloid neurotoxicity and neuroprotective role of 17β estradiol in aging rat brain synaptosomes

Abstract

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 beta-amyloid protein (Aβ). Accumulation of oligomeric Aβ in the brain contributes to neuronal dysfunction and ultimately leads to neurodegeneration. During aging the brain experiences structural, molecular, and functional alterations. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of neuropeptide, neurokinin B (NKB) and beta-amyloid 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. The aged rats (12 and 24 months old) (n= 8 for each group) were given subcutaneous injection of 17 b -estradiol (0.1 μg/g body weight) daily for one month. After 30 days of hormone treatment, experimental animals of all the groups were sacrificed and brains were isolated for further study. Aging brain function were assayed by measuring the activities of antioxidant enzymes, monoamine oxidase (MAO), membrane bound ATPases, intracellular calcium levels and lipid peroxidation in presence of neuropeptides. The results obtained in the present work revealed that i ncreased activities of antioxidant enzymes, membrane bound ATPases and decrease in level of calcium levels, MAO actiivty and lipid peroxidation in presence of NKB and combined NKB and Aβ in vivo estradiol (E2) treated ageing rat brain. NKB treatment reversed the beneficial in preventing some of the age related changes in the 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. Present study elucidates an antioxidant, neuromodulatory and neuroprotective role of tachykinin peptide NKB against the beta amyloid induced toxicity in E2 treated female rats. NKB treatment reversed the beneficial in preventing some of the age related changes in the brain.