Open Access Thesis
Valproic acid--Physiological aspects; Neurons--Effect of drugs on; Autism spectrum disorders;
Autism spectrum disorder has been dramatically on the rise since the early 1990s, with one in forty-five children being diagnosed in 2014. It is known that contributing factors to autism spectrum disorder may have genetic and epigenetic origins, as well as environmental triggers. What is still unclear, however, is the impact of teratogenic drugs, consumed by the mother, have on a developing fetus in utero. How can they lead to the child developing autistic-like behaviors? The current study documents the effects of one teratogenic drug Valproic acid, a known histone deacetylase inhibitor. It establishes the role it plays on developing neurites and synapses within the brain. This study supports Markram's proposal of an "intense world theory" characterized by autistic-like behaviors due to hyper-functioning microcircuits within the brain. Dorsal root ganglia were dissected out of eight day old chick embryos, some of which were exposed to varying concentrations of Valproic Acid, to serve as a model for this study. The dorsal root ganglia were cultured for 48 hours and then underwent a three day immunostaining procedure in order for their neurites and synapses to be observed clearly under the microscope. Composite images of each dorsal root ganglia were constructed using the tiling program ImagePro Premier. This program was also then used to count neurites and measure their lengths. Another program ImageJ was used to measure the area of synaptogenesis. Dorsal root ganglia exposed to Valproic Acid developed more and longer neurites when compared to controls. When exposed to a specific concentration they began to develop larger synaptogenic areas. These findings support Markram's "intense world theory" in demonstrating that in utero exposure to Valproic Acid may cause hyper-functioning synapses; begging to question as to whether or not other histone deacetylase inhibitors have the same effect.
Year of Submission
Master of Science
Department of Biology
1 PDF file (vii, 43 pages)
© 2017 - Hannah M. Bergan
Bergan, Hannah M., "Valproic acid: A neural outgrowth model for the autism spectrum disorder" (2017). Electronic Theses and Dissertations. 463.