Graduation Year

2022

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Science

Department

Neuroscience

Reader 1

Stacey Wood

Reader 2

Thomas Borowski

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Terms of Use for work posted in Scholarship@Claremont.

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© 2021 Elisabeth S Lawton

Abstract

Infantile Spasms (IS) is an epileptic disorder characterized by behavioral spasms in early life, seizures later in development, and cognitive deficits. IS affects 0.033% of live births (Dulla, 2018; Galanopoulou & Moshé, 2017). Anticonvulsants are ineffective against IS and the only available treatments are vigabatrin and adrenocorticotropic hormone (Pirone et al., 2017). Animal models are necessary to advance research that will elucidate etiologies and pharmacological interventions for IS. The APC cKO mouse is a novel model of IS in which the APC gene, a component of the β-catenin destruction complex in the canonical Wnt signaling pathway, is conditionally knocked out of excitatory forebrain neurons that express the protein CaMKIIα. APC cKO mice display neonatal spasms peaking at postnatal day 9 (P9), abnormal neonatal EEG, and adult seizures. This model was expected to target excitatory forebrain neurons and show early CaMKIIα expression. This study aimed to investigate the temporal and regional expression of CaMKIIα in mice over neonatal development and assessed the accuracy of the CaMKIIα promoter at targeting excitatory neurons in order to know when and where β-catenin levels increase in the APC cKO model. CaMKIIα expression increased over the developmental time window of P3 to P14 and was highly expressed in the striatum. There was no CaMKIIα expression in inhibitory interneurons, indicating that the CaMKIIα promoter is an accurate target for excitatory neurons. However, review of the literature showed that CaMKIIα is also expressed in inhibitory medium spiny neurons of the striatum. This study explored the implications of APC gene knockout in this population of neurons. Finally, this study concluded that the APC cKO mouse model is a proficient animal model of IS and elucidating its neural mechanisms may contribute to the understanding and treatment of Infantile Spasms.

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