Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis

Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis

Bibliographic Details
Main Author: Rolle, Isaiah J.
Language:English
Published: University of Cincinnati / OhioLINK 2015
Subjects:
Neurology
TEMPORAL LOBE EPILEPSY
HIPPOCAMPAL GRANULE CELLS
DENTATE GYRUS
PTEN
MTOR
HIPPOCAMPAL SEIZURES
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14488737592021-08-03T06:34:09Z Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis Rolle, Isaiah J. Neurology TEMPORAL LOBE EPILEPSY HIPPOCAMPAL GRANULE CELLS DENTATE GYRUS PTEN MTOR HIPPOCAMPAL SEIZURES 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. 2015 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Neurology
TEMPORAL LOBE EPILEPSY
HIPPOCAMPAL GRANULE CELLS
DENTATE GYRUS
PTEN
MTOR
HIPPOCAMPAL SEIZURES
spellingShingle Neurology
TEMPORAL LOBE EPILEPSY
HIPPOCAMPAL GRANULE CELLS
DENTATE GYRUS
PTEN
MTOR
HIPPOCAMPAL SEIZURES
Rolle, Isaiah J.
Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
author Rolle, Isaiah J.
author_facet Rolle, Isaiah J.
author_sort Rolle, Isaiah J.
title Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
title_short Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
title_full Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
title_fullStr Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
title_full_unstemmed Threshold for Hippocampal Dentate Granule Cell Mediated Epileptogenesis
title_sort threshold for hippocampal dentate granule cell mediated epileptogenesis
publisher University of Cincinnati / OhioLINK
publishDate 2015
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448873759
work_keys_str_mv AT rolleisaiahj thresholdforhippocampaldentategranulecellmediatedepileptogenesis
_version_ 1719439428287463424

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