Award Date

12-15-2019

Degree Type

Thesis

Degree Name

Master of Arts (MA)

Department

Psychology

First Committee Member

Rochelle Hines

Second Committee Member

Dustin Hines

Third Committee Member

Jefferson Kinney

Fourth Committee Member

Murray Millar

Number of Pages

84

Abstract

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can lead to the phenotypes seen in neurodevelopmental disorders, including seizures. To study this possibility, we performed morphological analyses of the AIS of cortical pyramidal neurons in mouse models of NDDs with a high incidence of epilepsy (Gabra2-1 and Mecp2+/-). Our results reveal morphological changes at the AIS of both, Gabra2-1 and Mecp2+/- mice, when compared to wild-type mice. Understanding neuropathological changes leading to these heterogeneous disorders will increase knowledge of the general underlying mechanisms thus contributing to the development of better therapies.

Keywords

comorbidity; GABA receptors; inhibition; mouse model mutation; Rett Syndrome; sodium channel

Disciplines

Biology | Cell Biology | Medical Neurobiology | Neuroscience and Neurobiology | Neurosciences

File Format

pdf

File Size

1.8 MB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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