Honors Program Theses
Valproic acid activates hyperactivity in cultured neurons: possible support for overconnectivity hypothesis of autism
Honors Program Thesis (UNI Access Only)
Valproic acid--Physiological effect; Neural networks (Neurobiology)--Effect of drugs on; Autism spectrum disorders--Etiology;
A leading hypothesis to explain the recent rise in diagnoses of autism spectrum disorder (ASD) is the “intense world” concept of neural overconnectivity, leading to brain overgrowth. Known environmental contributors to overconnectivity include valproic acid (VPA), an anti-seizure drug used to treat epilepsy, migraines and other conditions. VPA is commonly avoided during pregnancy when possible. Recent studies have linked VPA to increased risk for ASD. During embryonic development neurons form and send out threadlike neurites in search of connections. Neurites are led by expanded motile endings, exploratory growth cones, which seek connections to form synapses. Movement of growth cones with their array of tiny “microspikes” can be captured live, microscopically, in time-lapse and analyzed using image analysis software. We examined the effects of VPA on neurite and growth cone activity in order to evaluate any evidence for overconnectivity. To do this we dissected out and cultured dorsal root ganglia (DRGs) from 8-day old chick embryos. DRGs attach and begin to extend neurites with growth cones within 36 hours. Dishes with established DRGs were placed on the heated stage of an inverted microscope. Images were captured each minute for a time-lapse video using imaging software. After 30 minutes VPA was added to the culture medium from a stock solution to achieve 2 mM, a known effective concentration, and images were captured for another 30 minutes. Images in the video were then analyzed using ImageJ software to measure growth cone areas and neurite lengths in each frame. These were used to calculate growth cone area change per minute and net extension and retraction of neurites. Data provided evidence for an increase in average area change per minute of 63%, and an increase in net neurite extension of four-fold greater than the control following the addition of VPA. The data thus far provides support for a neural overconnectivity mechanism for VPA.
Year of Submission
Department of Biology
University Honors Designation
A thesis submitted in partial fulfillment of the requirements for the designation University Honors
1 PDF file (55 pages)
©2016 Alexis McGinley
McGinley, Alexis, "Valproic acid activates hyperactivity in cultured neurons: possible support for overconnectivity hypothesis of autism" (2016). Honors Program Theses. 224.