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Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis

Rolle, Isaiah J
http://orcid.org/0000-0001-5625-5553
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759

Abstract Details

2015, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
Patients with temporal lobe epilepsy are treated with anticonvulsant drugs that neither prevent nor cure the disease. The development of true anti-epileptogenic therapies will require a better understanding of the molecular mechanisms of epileptogenesis. Animal and human studies of temporal lobe epilepsy have long implicated newly-born dentate granule cells (DGCs) as mediating many of these epileptogenic changes. Work from our lab described in this report demonstrates that phosphatase and tensin homolog (PTEN) deletion need only occur in up to 25% of hippocampal DGCs to produce a severe epilepsy syndrome in mice. This was the first direct evidence provided to show that abnormal DGCs can cause the disease. It is also conceivable that a certain threshold level of abnormal cells must be reached to provoke epileptogenesis; but after this threshold is passed, additional abnormal cells have no further impact. We hypothesize that the severity of epilepsy is dependent on the number of abnormal DGCs in these animals, and we predict, therefore, that modifying the model to produce fewer abnormal cells will mitigate the disease phenotype. The second chapter, previously published in Neuron, details the selective deletion of PTEN from hippocampal granule cells. The third chapter directly tests our guiding hypothesis, whether deletion from a smaller number of DGCs, roughly 5% or less, is sufficient to cause epilepsy. In the fourth chapter, we will describe initial experiments that test whether and when electroencephalogram (EEG) abnormalities can be reversed by ablating irregular DGCs. These studies will provide novel insights into 1) the role these neurons play in chronic epilepsy, and 2) whether we can identify a therapeutic window to interfere with disease progression.
James Eliassen, Ph.D. (Committee Chair)
Mark Baccei, Ph.D. (Committee Member)
Kenneth Campbell, Ph.D. (Committee Member)
Steve Danzer, Ph.D. (Committee Member)
Darcy Krueger, M.D. Ph.D. (Committee Member)
154 p.
Neurology
TEMPORAL LOBE EPILEPSY; HIPPOCAMPAL GRANULE CELLS; DENTATE GYRUS; PTEN; MTOR; HIPPOCAMPAL SEIZURES

Recommended Citations

Citations

  • Rolle, I. J. (2015). Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759

    APA Style (7th edition)

  • Rolle, Isaiah. Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis. 2015. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759.

    MLA Style (8th edition)

  • Rolle, Isaiah. "Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis." Doctoral dissertation, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759

    Chicago Manual of Style (17th edition)

ucin1448873759
481
© 2015, some rights reserved.Creative Commons License Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis by Isaiah J Rolle is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.