Date of Award

January 2017

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Tamas Horvath

Second Advisor

Seth Guller


We previously observed an association between brain mitochondrial mechanisms in mouse pups and mode of delivery. We also demonstrated that alterations in mitochondria can impact adult behavior. In this study we hypothesized that vaginal delivery induces mitochondrial uncoupling protein 2 (UCP-2) expression in-vivo when compared to surgical delivery and differences in expression alter neurodevelopment and adult behavior. We examined the hippocampus and layer III of the prefrontal cortex of vaginally and surgically delivered mice and evaluated gene expression of UCP-2 and mitochondrial and synaptic density of these areas using electron microscopy. Additionally, we performed open field, elevated plus, Y-maze and pre-pulse inhibition testing. We found that vaginal delivery is associated with increased expression of UCP-2. Surgically delivered animals do not experience this induction and demonstrate changes in mitochondrial mechanisms and synaptogenesis in the hippocampus and prefrontal cortex into adulthood. These alterations in ultrastructure are associated with phenotypes resembling animal models of psychiatric illness such as hyperlocomotion, decreased anxiety, and decreased auditory gating. However, by knocking out UCP-2, mode of delivery is unable to render these changes in ultrastructure or behavior. These results highlight how adult neuronal circuitry and behavior are impacted by delivery dependent mitochondrial adaptations.


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