Thesis Format
Monograph
Degree
Master of Science
Program
Pathology and Laboratory Medicine
Supervisor
Zhang, Qi
Abstract
The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a “gate-like” function to the downstream Cornu Ammonis (CA) sectors. Despite this critical role, DG pathologies are not heavily considered in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, here we analyze hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Our data show distinct DG morphometry and RNA expression profiles between HS and no-HS. Interestingly, regardless of pathological diagnosis, the DG morphometry correlates with patient’s post-operative outcome. Our data indicates differential expression of pathways including neurogenesis, complement system, and matrix remodeling between HS and no-HS DG. This study reveals possible prognostic value in DG morphometry, as well as supports the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms.
Summary for Lay Audience
Epilepsy is one of the most common neurological disorders worldwide. Focal onset epilepsy occurs when seizure activity begins within a specific region of the brain. Epilepsy that is no longer controlled by anti-epileptic drugs may be referred for surgical removal of the tissue where seizure activity is observed to begin. This is most common in epilepsies beginning within the temporal lobe of the brain. The most frequent diagnosis of temporal lobe epilepsy cases is hippocampal sclerosis (HS). HS is characterized by loss of neurons within the hippocampus, a structure deep within the temporal lobe. HS can be divided into subtypes, including one called ‘no-HS’ where neuron loss is not observed. No-HS is currently associated with HS despite the vast differences seen when examining the two subtypes. These differences could indicate HS and no-HS are separate diseases. The dentate gyrus (DG) is a “gate-like” structure that is within the hippocampus, performing the critical role of allowing or disallowing input to enter other hippocampal regions. Despite this critical function, changes observed in the DG are not emphasized when diagnosing HS. In this study, we will further investigate cellular and gene expression differences within the DG of both HS and no-HS cases.
To further characterize DG cellular changes is HS and no-HS, I examined the DG in HS, no-HS, and control (non-temporal lobe epilepsy) cases using a software to evaluate cell physical characteristics. To investigate if HS and no-HS should be considered separate diseases, I removed the DG from HS and no-HS cases and performed an analysis of gene expression.
My results show that HS and no-HS have different DG cell characteristics, and that temporal lobe epilepsy cases that become seizure free after surgery also show different DG cell characteristics when compared to those that continue to have seizures after surgery. I also saw that HS and no-HS cases have differences in gene expression within the DG.
Overall, this study shows that analyzing the DG cells can help distinguish which patients will become seizure free after surgery. This study will also allow for a better understanding of differences between HS and no-HS.
Recommended Citation
Twible, Carolyn, "Characterizing the hippocampal dentate gyrus involvement in temporal lobe epilepsy" (2024). Electronic Thesis and Dissertation Repository. 10061.
https://ir.lib.uwo.ca/etd/10061
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.