Date of Graduation

Summer 2021

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Lyon Hough

Abstract

The neurotransmitter serotonin is involved in the early development of the central nervous system and the organization of neurons throughout the cerebral cortex and cerebellum. It is proposed that serotonin indirectly interacts with cells in the marginal zone of the cerebral cortex known as Cajal-Retizus (CR) cells. These cells secrete the extracellular matrix protein reelin, which is known for its role in neuronal organization and migration during early neural development. It has been observed that low levels of serotonin are associated with similarly low levels of reelin during development and have been reported to result in disorganization of neurons in the cortical layers. Similarly, neuronal disorganization of the cortex has also been reported in response to increased levels of developmental serotonin which in-turn can lower serotonin levels in the developed brain due to activation of an autoregulatory negative feedback mechanisms. For reelin to be secreted by the CR cells, the neurotransmitter γ-aminobutyric acid (GABA) needs to be available to interact with the GABAA receptor on the CR cells themselves. However, GABA is associated with the Glutamate/GABA excitatory and inhibitory feedback system where high levels of glutamate will stimulate release of GABA and vice versa. These neurotransmitters regulate the activity of many key processes such as overall excitation of the brain and is proposed to have a role in the organization and migration of neurons during development. It is known that serotonin is the early regulator of glutamate release in the cell which in turn activates the release of GABA. However, it is thought that in conditions where excess serotonin is released during development (hyperserotonemia) that serotonin will inhibit glutamate release instead of activation. This study proposes to investigate the methodological processes necessary to analyze the correlation of excess developmental serotonin on the neurotransmitter glutamate. This was conducted by identifying the dorsal raphe nuclei via cresyl violet staining on control Sprague-Dawley rat brain tissues while investigation of glutamate release levels in development was performed via immunohistochemical labeling of vesicular glutamate transporters in the dorsal raphe nuclei.

Keywords

Autsim Spectrum Disorder (ASD), developmental hyperserotonemia (DHS), Cajal-Retizus cells, reelin, serotonin, cortical development

Subject Categories

Cell Biology | Developmental Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience | Molecular Biology

Copyright

© Trey M. Shupp

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