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Yermakov LM_Dissertation.pdf (2.93 MB)

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Type 2 Diabetes Leads to Impairment of Cognitive Flexibility and Disruption of Excitable Axonal Domains in the Brain

Yermakov, Leonid M.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1559401756413422

Abstract Details

2019, Doctor of Philosophy (PhD), Wright State University, Biomedical Sciences PhD.
Type 2 diabetes is a metabolic disease affecting millions of people around the world. Cognitive and mood impairments are among its many debilitating complications, but disease mechanism(s) remain elusive. Here, we present a series of behavioral tasks that demonstrate impairment of cognitive flexibility in db/db mice, a commonly used type 2 diabetes model. Using immunohistochemistry, we demonstrate disruption of axon initial segments (AIS) and nodes of Ranvier, excitable axonal domains regulating neuronal output, in brain regions associated with cognitive and mood impairments. Finally, we present results of exercise treatment that ameliorates AIS disruption in these animals. Establishing cognitive flexibility deficits in db/db mice that parallel disease complications in patients with type 2 diabetes allows future research to test novel treatment strategies, while discovering disruption of excitable axonal domains fills the missing gap in our understanding of disease pathophysiology.
Keiichiro Susuki, M.D., Ph.D. (Advisor)
Mark M. Rich, M.D., Ph.D. (Committee Member)
Kathrin L. Engisch, Ph.D. (Committee Member)
Khalid M. Elased, Pharm.D., Ph.D. (Committee Member)
Lynn K. Hartzler, Ph.D. (Committee Member)
114 p.
Behavioral Sciences; Biomedical Research; Neurosciences
cognitive flexibility; Morris water maze; axon initial segment; node of Ranvier; medial prefrontal cortex; hippocampus; type 2 diabetes; exercise; db db mice

Recommended Citations

Citations

  • Yermakov, L. M. (2019). Type 2 Diabetes Leads to Impairment of Cognitive Flexibility and Disruption of Excitable Axonal Domains in the Brain [Doctoral dissertation, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1559401756413422

    APA Style (7th edition)

  • Yermakov, Leonid. Type 2 Diabetes Leads to Impairment of Cognitive Flexibility and Disruption of Excitable Axonal Domains in the Brain. 2019. Wright State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1559401756413422.

    MLA Style (8th edition)

  • Yermakov, Leonid. "Type 2 Diabetes Leads to Impairment of Cognitive Flexibility and Disruption of Excitable Axonal Domains in the Brain." Doctoral dissertation, Wright State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1559401756413422

    Chicago Manual of Style (17th edition)

wright1559401756413422
318
© 2019, some rights reserved.Creative Commons License Type 2 Diabetes Leads to Impairment of Cognitive Flexibility and Disruption of Excitable Axonal Domains in the Brain by Leonid M. Yermakov is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Wright State University and OhioLINK.