Abstract Title:

17α-estradiol attenuates neuron loss in ovariectomized Dtg AβPP/PS1 mice.

Abstract Source:

J Alzheimers Dis. 2011;23(4):629-39. PMID: 21157032

Abstract Author(s):

Kebreten F Manaye, Joanne S Allard, Sara Kalifa, Amy C Drew, Guang Xu, Donald K Ingram, Rafael de Cabo, Peter R Mouton

Article Affiliation:

Department of Physiology&Biophysics, College of Medicine, Howard University, Washington, DC 20059, USA. [email protected]

Abstract:

Quantitative microanalysis of brains from patients with Alzheimer's disease (AD) find neuronal loss and neuroinflammation in structures that control cognitive function. Though historically difficult to recapitulate in experimental models, several groups have recently reported that by middle-age, transgenic mice that co-express high levels of two AD-associated mutations, amyloid-β protein precursor (AβPP(swe)) and presenilin 1 (PS1(ΔE9)), undergo significant AD-type neuron loss in sub-cortical nuclei with heavy catecholaminergic projections to the hippocampal formation. Here we report that by 13 months of age these dtg AβPP(swe)/PS1(ΔE9) mice also show significant lossof pyramidal neuron in a critical region for learning and memory, the CA1 subregion of hippocampus, as a direct function of amyloid-β (Aβ) aggregation. We used these mice to test whether 17α-estradiol (17αE2), a less feminizing and non-carcinogenic enantiomer of 17β-estradiol, protects againstthis CA1 neuron loss. Female dtg AβPP(swe)/PS1(ΔE9) mice were ovariectomized at 8-9 months of age and treated for 60 days with either 17αE2 or placebo via subcutaneous pellets. Computerized stereology revealed that 17αE2 ameliorated the loss of neurons in CA1 and reduced microglial activation in the hippocampus. These findings support the view that 17αE2, which may act through non-genomic mechanisms independent of traditional estrogen receptors, could prevent or delay the progression of AD in older men and women.

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