Synaptic dysfunction is a critical neuropathological feature prior to the formation of extracellular senile plaques and intracellular fibrillary tangles (NFTs) in Alzheimer’s disease (AD). The synapse loss and neurites impairment lead to synaptic dysfunction that can be induced by oligomeric Aβ. The administration of oligomeric Aβ reduced the pre-synaptic vesicle proteins and altered the cytoskeletal proteins. The synaptic vesicles (SVs) playing a crucial role to transport and recycle the SV proteins and neurotransmitters (NTs) in synaptic terminals. However, the uptake and release capabilities of SVs were also disrupted by oligomeric Aβ. The disruption of SVs recycling and neurites impairment attenuate neurotransmission that exacerbates the pathogenesis of AD. Therefore, any agents can maintain the SVs recycling and protect the neurites development that could be a therapeutic target for AD. Testosterone is a male sex steroid hormone, which is a potent therapeutic drug for neurodegenerative diseases. It has been found the neuroprotective effects for neuronal death, but the implication on synaptoprotection is still not clear. This study investigated the neuroprotective effects of testosterone from oligomeric Aβ-induced synaptic dysfunction in primary cultured hippocampal neurons. My study demonstrated that testosterone prevented Aβ-induced reduction of pre-synaptic proteins and shortening neurites. Also, testosterone could protect SVs recycling by increasing SVs unloading capability via estrogenic independent pathway. The findings reinforce the neuroprotective effects of testosterone. They are probably facilitating future development for using the concept of male sex hormone as therapy and the intervention of therapeutic drugs for AD patients. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

The purpose of this study was to examine the effects of androstenedione supplementation on testosterone levels in older men. Healthy men (n = 11) between the ages of58 and 69 were divided into two groups: 6 taking 300 mg of androstenedione (mean ± SE, 62.33 ± 2.57) supplement and 5 taking the 300 mg cellulose placebo (mean ± SE, 60.2 ± 1.02) for a period of seven days. Subjects in both groups had been participating in the Ball State University Adult Fitness Program (BSUAFP) for at least one year, incorporating both aerobic and resistance training into their workouts. Testing measures involved the subjects performing two exercises (leg extension and leg curl) while having blood drawn prior to, during, and post-exercise for a period of 20 minutes both pre-and post-supplementation. Specific weights for the subjects were determined with a ten-repetition maximum (10-RM) lift on both exercises. It appeared that the subjects in the androstenedione group were stronger with the exercises than the subjects in the placebo group, but with no significance. Testosterone, estradiol, and androstenedione were analyzed via hormone assay pre-and post-supplementation. The analysis of the testosterone revealed a significant difference pre-(mean ± SE, 4.65 ± .51 ng/ml) to post-(mean ± SE, 6.72 ± .58 ng/ml) supplementation for the androstenedione group. Analysis of the androstenedione revealed a significant difference pre-(mean ± SE, 0.88 ± .20) to post-(mean ± SE, 7.46 ± 1.25) supplementation for the androstenedione group. The estradiol assay revealed no significant differences pre-to post-supplementation for either group. The placebo group did not demonstrate any significant differences pre-to post-supplementation for either testosterone or androstenedione. The results of this study concluded that supplementation with 300 mg. of androstenedione for a period of seven days significantly elevated blood testosterone in older men. / School of Physical Education

Graduation date: 1992