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- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a Blank IUD (without Levo), or a Levo-releasing IUD (Levo IUD), enabling us to evaluate the effects of Ovx and the effects of IUD administration on cognition. Two weeks after surgery, all treatment groups were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. At sacrifice, upon investigation of the uteri, it was determined that some of the IUDs were no longer present in animals from these groups: Sham\u2014Blank IUD, Ovx\u2014Blank IUD, and Sham\u2014Levo IUD. Results from the remaining three groups showed that compared to Sham animals with no IUDs, Ovx animals with no IUDs had marginally impaired working memory performance, and that Ovx animals with Levo IUDs as compared to Ovx animals with no IUDs had marginally enhanced memory performance, not specific to a particular memory type. Results also showed that Ovx animals with Levo IUDs had qualitatively more cells in their vaginal smears and increased uterine horn weight compared to Ovx animals with no IUDs, suggesting local stimulation of the Levo IUDs to the uterine horns. Overall, these results provide alternative evidence to the hypothesis that the Levo IUD administers Levo in solely a localized manner, and suggests that the possibility for the Levo IUD to affect reproductive cyclicity in ovary-intact animals is not rejected. The potential for the Levo IUD to exert effects on cognition suggests that either the hormone does in fact systemically circulate, or that the Levo IUD administration affects cognition by altering an as yet undetermined hormonal or other feedback between the uterus and the brain.
ContributorsStrouse, Isabel Martha (Author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Sirianni, Rachael (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.
ContributorsCeton, Ricki Ronea (Author) / Stabenfeldt, Sarah (Thesis director) / Sirianni, Rachael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05