Early intervention with an estrogen receptor ?-selective phytoestrogenic formulation prolongs survival, improves spatial recognition memory, and slows progression of amyloid pathology in a female mouse model of Alzheimer's disease.

ABSTRACT: Our recent developments have yielded a novel phytoestrogenic formulation, referred to as the phyto-?-SERM formulation, which exhibits an 83-fold binding selectivity for the estrogen receptor subtype ? (ER?) over ER?. Earlier studies indicate that the phyto-?-SERM formulation is neuroprotective and promotes estrogenic mechanisms in the brain while devoid of feminizing activity in the periphery. Further investigation in a mouse model of human menopause indicates that chronic exposure to the phyto-?-SERM formulation at a clinically relevant dosage prevents/alleviates menopause-related climacteric symptoms. This study assessed the efficacy, in an early intervention paradigm, of the phyto-?-SERM formulation in the regulation of early stages of physical and neurological changes associated with Alzheimer's disease (AD) in a female triple transgenic mouse model of AD. Results demonstrated that, when initiated prior to the appearance of AD pathology, a 9-month dietary supplementation with the phyto-?-SERM formulation promoted physical health, prolonged survival, improved spatial recognition memory, and attenuated amyloid-? deposition and plaque formation in the brains of treated AD mice. In comparison, dietary supplementation of a commercial soy extract preparation showed no effect on cognitive measures, although it appeared to have a positive impact on amyloid pathology. In overall agreement with the behavioral and histological outcomes, results from a gene expression profiling analysis offered insights on the underlying molecular mechanisms associated with the two dietary treatments. In particular, the data suggests that there may be a crosstalk between ER? and glycogen synthase kinase 3 signaling pathways that could play a role in conferring ER?-mediated neuroprotection against AD. Taken together, these results support the therapeutic potential of the phyto-?-SERM formulation for prevention and/or early intervention of AD, and warrants further investigations in human studies.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC4197935 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature