Degree Type
Honors Capstone Project
Date of Submission
Spring 5-1-2018
Capstone Advisor
James Hewett
Honors Reader
Sandra Hewett
Capstone Major
Biology
Capstone College
Arts and Science
Audio/Visual Component
no
Capstone Prize Winner
no
Won Capstone Funding
yes
Honors Categories
Sciences and Engineering
Subject Categories
Biology | Life Sciences
Abstract
Cyclooxygenase-2 (COX-2) is one of two COX enzymes involved in the conversion of free arachidonic acid (AA) to prostaglandin H2, a precursor for prostaglandin synthesis. COX-2 expression has been detected in the cerebral cortex, hippocampal formation, and amygdala, with its expression localized to the dendritic spines of excitatory neurons. In addition to its localization in excitatory neurons, COX-2 expression is regulated by neuronal activity, suggesting a modulatory role of COX-2 in synaptic transmission. COX-2 contributes to numerous functions in the normal brain, including learning and memory. Findings from our lab suggest that COX-2 also contributes to the maintenance of the seizure threshold, which is an innate property of the brain that depends on the homeostatic balance between excitation and inhibition. For example, pharmacological inhibition of COX-2 increased and neuronal overexpression of COX-2 in the CNS decreased the severity and incidence of convulsive seizures. Voluntary exercise has also been shown to play a role in reducing seizure frequency and severity. However, the mechanism behind how it does so remains poorly understood. The elevated seizure threshold that results from both elevated COX-2 levels and exercise potentially suggests that changes in COX-2 expression mediate the effects of running on the seizure threshold. Here I hypothesize that running will increase the expression of COX-2 in the hippocampus, resulting in increased prostaglandin production that will in turn raise the seizure threshold. To test this, CD-1 mice were housed in running wheel cages for 4 weeks before testing the seizure threshold. Seizures were induced through the use of pentylenetetrazole (PTZ) and scored based on their severity as a measure of the seizure threshold. To measure COX-2 expression and activity, brain tissue samples were collected for COX-2 immunostaining and assayed for Prostaglandin E2, a downstream product of COX-2 activity. While COX-2 expression and PGE2 levels were elevated after running, we did not see an elevation of the seizure threshold in mice belonging to the running wheel experimental group. However, unlike other studies examining the effects of running on the seizure threshold, tests of the seizure threshold in the current study were performed six days post running rather than immediately after running had concluded. The difference in the results presented here from those reported previously could suggest that the effects of exercise on the seizure threshold are transient and require ongoing participation.
Recommended Citation
Kerker, Kylie, "Influence of Running on the Seizure Threshold" (2018). Renée Crown University Honors Thesis Projects - All. 1175.
https://surface.syr.edu/honors_capstone/1175
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