Bound Volume Number
Honors Capstone Project
Date of Submission
Prof. James Hewett
Prof. Kari Segraves
Arts and Science
Neurogenesis, dentate gyrus (DG), hippocampus, neuroplasticity
Capstone Prize Winner
Won Capstone Funding
Sciences and Engineering
Molecular and Cellular Neuroscience
Neurogenesis, the generation of new neurons, is most prevalent when the brain is being formed during pre-natal development. However, this process continues in select areas in the brain during adult life as well. One such area in the brain is the dentate gyrus (DG) of the hippocampus, an area known to be associated with learning and memory. In this region, neurogenesis is believed to contribute to neuroplasticity as well as improving its functions in learning and memory. Interestingly, this synthesis of neurons is increased by physical activity—predominantly running—and by seizures originating in the limbic system. The increased excitatory neuronal activity that occurs during a seizure leads to an increase in an enzyme called cyclooxygenase-2 (COX-2), the initial enzyme in the production of prostaglandins from arachidonic acid. COX-2 is usually expressed in certain neurons of the brain including the CA3 subregion of the hippocampus, and its level of expression is linked to increased excitatory neuronal activity. In other words, COX-2 is up-regulated by seizure activity; therefore, during seizures there is an increase in COX-2 activity and expression. Because new neurons exhibit increased excitatory responsiveness, the goal of this research is to test the possibility that exercise-induced new neurons of the DG will exhibit increased COX-2 levels following acute seizure activity. It is predicted that it will, and amplified COX-2 levels will be found in subjects that have access to physical exercise, particularly in the new neurons generated by running. An experimental group of mice were supplied with running wheels and allowed to run for roughly one month. Bromodeoxyuridine (BrdU) was injected one week after the start of running in order to label the newly generated neurons in the hippocampus. After running, animals were subjected to acute seizures through pentylenetetrazol (PTZ) injections, and the subsequent seizures were scored based on severity. Cardiac perfusions were then performed to collect brain tissue that was then coronally sectioned using the cryostat and mounted on microscope slides, in order to stain for COX-2 and BrdU. Running mice exhibited lower seizure scores than control mice implying that the neurogenesis induced by physical activity increased the COX-2 levels, thus raising the seizure threshold in exercised mice.
Kim, Gina, "Exercise-Induced Adult Neruogenesis and the Seizure Threshold: the Role of COX-2" (2015). Honors Capstone Projects - All. 848.
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