Publication Date
2022
Document Type
Thesis
Committee Members
Keiichiro Susuki, M.D., Ph.D. (Advisor); Sherif M. Elbasiouny, Ph.D., P.E. (Committee Member); David R. Ladle, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Cognitive impairment is a serious global health issue due to its widely complicated pathologies that are linked to many diseases, including type 2 diabetes. Yet, detailed mechanisms of cognitive impairment associated with type 2 diabetes are unknown. Evidence suggests type 2 diabetes is associated with disrupted glucose metabolism, elevated methylglyoxal, and axon initial segment (AIS) shortening. Subtle changes of AIS could significantly contribute to neuronal dysfunction in neurological diseases (e.g., cognitive impairment). Utilizing in vitro dissociated mouse cortical cultures, we initially discovered elevated methylglyoxal shortens the AIS length of the immunofluorescent marker AnkyrinG (Griggs et al., 2021). This thesis further elucidated mechanisms of methylglyoxal-induced AIS shortening in vitro. Particularly, AIS shortening by methylglyoxal is not induced by methylglyoxal-mediated cell death or its neurotoxic metabolized D-lactate. Rather, methylglyoxal shortens AIS via calpain signaling, but not calcineurin. These results provide important insights into mechanisms of cognitive impairment linked with type 2 diabetes.
Page Count
83
Department or Program
Department of Neuroscience, Cell Biology, and Physiology
Year Degree Awarded
2022
Copyright
Copyright 2022, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may not be modified. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
ORCID ID
0000-0003-2275-2193
