IN VITRO MODELS OF NEURONAL DEVELOPMENT IN VIVO EXHIBIT STRUCTURAL PLASTICITY AND CAN PROVIDE INSIGHT INTO NEURODEVELOPMENTAL DISORDERS SUCH AS SCHIZOPHRENIA
Open Access
- Author:
- Blandin, Elisabeta
- Graduate Program:
- Neuroscience
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- December 19, 2018
- Committee Members:
- Alfredo Bellon, Thesis Advisor/Co-Advisor
Andras Hajnal, Committee Member
Patricia Sue Grigson-Kennedy, Committee Member - Keywords:
- Neurostructure
Dynamic
Dopamine
Schizophrenia
Neuroblastoma - Abstract:
- Schizophrenia is a debilitating neuropsychiatric disorder that affects about one percent of the population worldwide. For decades, researchers have been investigating its etiology without success. However, there is consistent data indicating that patients experience a reduction in cortical volume likely due to shorter neuronal extensions. The neurotransmitter dopamine has also been commonly associated with this psychotic disorder but its role remains elusive. At the same time, mounting evidence indicates that schizophrenia is a neurodevelopmental illness. It has yet to be determined whether there is an association between these apparently unrelated findings. Our main hypothesis is that schizophrenia is a neurodevelopmental disorder caused, at least in part, by a faulty neurostructural response to dopamine during development. The aim of this study is to show that human neuroblastoma cells present dynamic structural changes similar to what is known to occur during normal brain development. In addition, we aim to demonstrate that dopamine has a direct influence on these dynamic structural changes. Our results indicate that human neuroblastoma cells of the line SH-SY5Y present dynamic structural changes in vitro that increase when cells are differentiated with retinoic acid. However, treatments with various concentrations of colchicine, a toxin known to affect the cytoskeleton, failed to impact these structural changes. Likewise, different concentrations of dopamine did not modify the structural plasticity observed in these cells and did not exhibit any directional bias with regard to retraction and extension. It is possible that longer incubation times with dopamine could have influenced the dynamic structural changes seen in neuroblastoma cells. It is also likely that chemicals known to alter the actin cytoskeleton could have impacted the neuronal structure.