Hypothalamic and hippocampal mechanisms linking epilepsy and comorbid reproductive endocrine dysfunction

Reproductive endocrine comorbidities occur in people with epilepsy at rates significantly higher than the general population. Comorbid reproductive endocrine dysfunction is particularly prevalent in temporal lobe epilepsy, which is the most common form of focal epilepsy in adults. Previous work has shown that the intrahippocampal kainic acid mouse model (IHKA) of temporal lobe epilepsy recapitulates the disrupted reproductive cycle sometimes seen in clinical settings. Follow-up studies found that increased GnRH neuron firing activity was specific to IHKA females with long or disrupted cycles (KA-long) and was not present in IHKA females maintaining regular cycles (KA-regular). Throughout the initial chapters of this dissertation, potential causes of altered GnRH neuron firing activity were investigated. Initial studies showed a glutamate-dependent increase in excitatory GABA transmission to GnRH neurons in KA-long but not KA-regular females, indicating that the increased transmission was specific to those females with both epilepsy and comorbid cycle disruption. Later work investigated kisspeptin neurons in the anteroventral periventricular region (AVPVKiss) as a potential source of altered GABA transmission to GnRH neurons. Preliminary results showed that AVPVKiss neuron firing activity is increased in IHKA females. A final study took a different approach and aimed to distinguish between KA-long and KA-regular females using hippocampal EEG data as opposed to the patch clamp recordings used in earlier studies. Here, it was found that modern machine learning methods can differentiate between females with and without comorbid reproductive cycle disruption with a high degree of accuracy. Surprisingly, investigation of the model’s preferred metrics showed that measures related to EEG waveforms were more predictive than seizure burden, time of day, or estrous cycle stage.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Ingram, Robbie

Contributors dc:contributor

• Christian-Hinman, Catherine
• Raetzman, Lori
• Llano, Daniel
• Gritton, Howard

• Epilepsy
• Endocrine
• Reproductive

Statement dc:rights

• Copyright 2024 Robbie Ingram

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/124380

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F124380