Sepsis Survival Results in Synergistic Behavioral Deficits in Young 5xFAD Mice

Undergraduate #108
Discipline: Social, Behavioral, and Economic Sciences
Subcategory: Cell and Molecular Biology
Session: 1
Room: Park Tower 8216

Marc-Antonio Padilla - Oberlin College
Co-Author(s): Benjamin H Singer, University of Michigan, MI

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Survivors of sepsis commonly develop cognitive and affective disorders. Furthermore, hospitalization for acute illness is frequently a pivotal point in the progression of dementia in patients with Alzheimer’s disease (AD). However, the cognitive decline associated with sepsis survivorship is poorly understood. We hypothesize that sepsis survival will have greater behavioral effects in the presence of AD neuropathology in the normal brain. We used presymptomatic 5XFAD mice (4 months old) as a model of early Alzheimer?s Disease (AD) to investigate interactions between the behavioral deficits associated with sepsis survival and AD. Cecal ligation and puncture (CLP) was used as a naturalistic model of sepsis, and mice were tested at least 14 days after CLP. Previous studies in our laboratory have not demonstrated clear memory deficits in hippocampal based tasks such as the Morris water maze and contextual fear conditioning in wild-type sepsis survivor and na?ve mice. We therefore conducted behavioral testing on wild-type CLP survivor and 5xFAD CLP survivor mice using the puzzle box task, a measure of executive function that involves multiple brain regions including the prefrontal cortex, thalamic nuclei, hypothalamus, and cerebellum, in addition to contextual fear conditioning. 5xFAD sepsis survivor mice performed worse in the puzzle box task than wild-type sepsis survivor mice (Cox regression, p = 0.07). In the fear conditioning task, 5xFAD exhibited increased freezing in response to the conditioned context and increased generalization of conditioned fear compared to wild-type sepsis survivors (p < 0.02). Together, the results indicate an increased vulnerability of 5xFAD mice to both decline in executive function and affective disorders associated with sepsis survival. Future research direction includes glial analysis to investigate possible neuroinflammatory mechanisms.

Funder Acknowledgement(s): This work is supported by an NSF BIO REU award (#1852074) to Keith Duncan and Shelly Flagel of the Neuroscience Graduate Program of University of Michigan.

Faculty Advisor: Benjamin H Singer, singerb@med.umich.edu

Role: I performed the behavioral testing of the mice in the puzzle box task and the contextual fear conditioning.