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| author | Brianna C Donofrio |
| title | Modeling Music Therapy in an Alzheimers Disease Cell Culture System through the use of BDNF and LM11A-31 |
| abstract | Alzheimer's disease (AD) is a form of dementia that impairs memory and mental functioning by disrupting
neuronal metabolic processes (Selkoe 2001). One molecular system which is downregulated in the brain of AD patients is the neurotrophin, BDNF,
and its main receptor tyrosine kinase, TrKB (Arancibia et al. 2008). In contrast, the p75 receptor, which is normally stimulated by proBDNF
(uncleaved form of BDNF) and can lead to neuronal toxicity, is upregulated in AD patients and is one of the targets for amyloid beta (Dechant
and Barde 2002). Recently, scientists have begun to explore potential therapies for AD such as the use of music which has the potential to
stimulate cognitive functioning of the elderly (Simmons-Sterna 2010). Research in animal models suggests that BDNF can be enhanced by music
exposure (Angelucci et al. 2007b). In addition, scientists have synthesized an exogenous p75 receptor ligand, LM11A-31, which may be able to
shift neurons toward a survival pathway (Yang et al. 2008). In the present study, an Alzheimer's disease primary cortical neuronal culture
model was created via the addition of amyloid beta or excess glutamate in order to test the potential interaction between BDNF and LM11A-31.
Cell survival rates were based on an MTS Assay and neuronal morphology was characterized by tubulin staining. Cells were treated with BDNF
and LM11A-31 in order to test the effects of these compounds on percent cell survival and relative tubulin staining of the neurons. The interaction
between BDNF and LM11A-31 was also tested. The combined effects of BDNF and LM11A-31 decreased cell survival rates in most experiments, but this
was not consistent across all testing conditions and therefore the data was inconclusive. Future studies will need to examine BDNF and LM11A-31
separately and in combination to gain a more complete understanding of these compounds as potential therapies for Alzheimer's disease. |
| school | The College of Liberal Arts, Drew University |
| degree | B.A. (2017) |
| advisor | Dr. Roger Knowles |
| committee | Dr. Christina McKittrick
Dr. Leslie Sprout |
| full text | BCDonofrio.pdf |
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