Oxidative stress has been implicated in a variety of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and stroke. Estrogens are gonadal steroid hormones that have been shown to be neuroprotective against numerous in vitro and in vivo challenges. Evidence from epidemiological studies has shown the beneficial effects of estrogens against cognitive decline and memory loss. Integrins are cell surface receptors shown to have an important role in neural development and synaptic plasticity. This study hypothesized integrins to be one of the molecular targets for estrogen-mediated effects in the brain. The hypothesis was tested with a set of in vitro experiments using HT-22 cells and an in vivo study using an ovariectomized rodent model. In the in vitro study, oxidative stress induced by H2O2 caused an increase in the expression of β1-integrin protein while 17β-estradiol (E2) treatment along with H2O2 attenuated the increase in integrin expression. Nanomolar concentrations of E2 treatment increased the expression of integrins and showed a time-dependent increase in expression of integrins in HT-22 cells. In the in vivo study, E2 treatment caused an increase in the expression of post-synaptic proteins, post-synaptic density-95 (PSD-95) and N-methyl D-aspartate receptor subunit 1 (NMDAR1) in hippocampus and no significant differences were observed in the expression of pre-synaptic protein, synaptophysin and β1-integrins. Collectively, H2O2 and physiological concentrations of E2 affected the expression of β1-integrins in vitro but E2 did not have an effect on the expression of integrins in vivo. Effects of E2 on synaptic proteins do not appear to be mediated by β1-integrins.
|Advisor:||Simpkins, James W.|
|Commitee:||Dory, Ladislav, Sumien, Nathalie, Yang, Shaohua|
|School:||University of North Texas Health Science Center at Fort Worth|
|Department:||Pharmacology and Neuroscience|
|School Location:||United States -- Texas|
|Source:||MAI 47/05M, Masters Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Pharmacology|
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