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P4–415: The effect of moxibustion on spatial memory of aging rats and the underlying mechanisms
Author(s) -
Du Yan-Jun,
Tian Qing,
Sun Guo-Jie,
Wang Jian-Zhi
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2157
Subject(s) - moxibustion , morris water navigation task , medicine , hippocampal formation , apoptosis , hippocampus , neuron , acupuncture , pathology , biology , biochemistry , psychiatry , alternative medicine
through activation of both ER and ER . Objective: The goal of this research is to investigate the impact of ER or ER -selective phytoestrogens and select combinations on neuronal survival and morphogenesis, and ultimately, develop a formulation with efficacy to promote cognition and prevent age-related neurodegeneration associated with AD. Methods & Results: Using in silico molecular docking and physicochemical properties analyses followed by a competitive binding assay, we have identified a series of ER or ER -selective plant-derived estrogenic molecules (so we called PhytoSERMs) from a natural source chemical database. Five candidate PhytoSERMs that have the greatest binding selectivity for ER were assessed for their neuroprotective efficacy in primary cortical neurons. Dose-response analyses indicated that individually each of the 5 candidate PhytoSERMs was moderately protective against supraphysiological glutamate-induced neurotoxicity determined by LDH measurements, with the greatest neuronal response occurring at 100 nM 1 M. Western blot analyses demonstrated that 4 out of 5 candidate PhytoSERMs significantly increased the expression of the anti-apoptotic protein, Bcl-2, in neurons. Further analyses demonstrated that combined use of these candidate PhytoSERMs induced significantly increased neuroprotective efficacy compared to single components. Co-administration of all 4 candidate PhytoSERMs induced the maximal protection against glutamate-induced loss in neuron metabolic viability determined by Calcein AM assay, with an efficacy significantly greater than that induced by 17 -estradiol. We are currently investigating the impact of these PhytoSERMs and combined formulations on neuronal morphogenesis, a marker of neuroplasticity associated with memory function. Conclusions: These results contribute to generating conclusive proof of principle that an ER -selective PhytoSERM formulation could serve as an effective alternative to estrogen therapy for sustaining neurological health, function and prevention of AD.