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Journal of Aging Research
Volume 2013 (2013), Article ID 538979, 11 pages
http://dx.doi.org/10.1155/2013/538979
Research Article

Letrozole Potentiates Mitochondrial and Dendritic Spine Impairments Induced by β Amyloid

Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, Canada H3G 1Y6

Received 5 March 2013; Accepted 18 June 2013

Academic Editor: Holly M. Brown-Borg

Copyright © 2013 P. K.-Y. Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Reduced estrogens, either through aging or postsurgery breast cancer treatment with the oral nonsteroidal aromatase inhibitor letrozole, are linked with declined cognitive abilities. However, a direct link between letrozole and neuronal deficits induced by pathogenic insults associated with aging such as beta amyloid ( ) has not been established. The objective of this study was to determine if letrozole aggravates synaptic deficits concurrent with insult. We examined the effects of letrozole and oligomeric treatment in dissociated and organotypic hippocampal slice cultures. Changes in glial cell morphology, neuronal mitochondria, and synaptic structures upon letrozole treatment were monitored by confocal microscopy, as they were shown to be affected by oligomers. Oligomeric or letrozole alone caused decreases in mitochondrial volume, dendritic spine density, synaptophysin (synaptic marker), and the postsynaptic protein, synaptopodin. Here, we demonstrated that mitochondrial and synaptic structural deficits were exacerbated when letrozole therapy was combined with treatment. Our novel findings suggest that letrozole may increase neuronal susceptibility to pathological insults, such as oligomeric in Alzheimer’s disease (AD). These changes in dendritic spine number, synaptic protein expression, and mitochondrial morphology may, in part, explain the increased prevalence of cognitive decline associated with aromatase inhibitor use.