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BioMed Research International
Volume 2014, Article ID 103906, 12 pages
Research Article

Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric -Amyloid Peptide in Primary Culture of Hippocampal Neurons

1Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, Room L1-49, 21 Sassoon Road, Pokfulam, Hong Kong
2State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau
3Institute of Chinese Medicinal Science, University of Macau, Macau
4Department of Psychiatry, LKS Faculty of Medicine, Hong Kong
5Department of Ophthalmology, LKS Faculty of Medicine, Hong Kong
6Shenzhen Centre for Disease Control and Prevention, Shenzhen, China
7Division of Geriatric, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, SAR, Hong Kong
8Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, Hong Kong
9State Key Laboratory of Brain and Cognitive Sciences, Hong Kong

Received 15 March 2014; Revised 14 May 2014; Accepted 14 May 2014; Published 18 June 2014

Academic Editor: Jin-Tai Yu

Copyright © 2014 Chi-Fai Lau 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.


Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by -amyloid (A), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric A-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric A could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. A also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated A-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate A-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on A-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.