Poster abstracts
Poster number 104 submitted by Ale Zaleta Lastra
Synergistic effects of early life adversity and adult traumatic brain injury on microglia and behavior
Alejandra Zaleta Lastra (Neuroscience Graduate Program), Payton Puryear, Minna Mohamed, Miranda McDonald (Department of Psychology ), Rebecca Boland, Christopher Cotter, Sam Houle (Neuroscience Graduate Program), Zachary Zimomra , Olga N. Kokiko-Cochran (Department of Neuroscience, Center for Brain Injury Research and Discovery, Institute of Brain, Behavior, and Immunology), Kathryn M. Lenz (Department of Psychology, Department of Neuroscience, Institute of Brain, Behavior, and Immunology, Center for Brain Injury Research and Discovery)
Abstract:
Background: Early life adversity (ELA) is a public health concern. 64% of U.S. adults report ELA, which is linked to 30% of later-life psychiatric conditions. Traumatic brain injury (TBI) affects ~2 million Americans annually. TBI following ELA increases risk for mood disorders, suggesting synergistic effects on long term outcomes. ELA in rodent models perturbs microglia engulfment of synapses, leading to altered synaptic neurodevelopment. ELA also leads to microglia priming, which may alter their response to secondary insults, including TBI. Here, we investigated whether ELA and TBI alter microglia and behavioral outcomes, and if microglia turnover after ELA mitigates mood-related behavioral alterations following adult TBI.
Methods: Male and female mouse pups underwent 4 hr/day of maternal separation stress, a rodent model of ELA, from postnatal day (P)1-14 or were left undisturbed (n=6-8). ELA dams underwent daily unpredictable stress from P1-14. At weaning, mice were treated for 7 days with CSFR-1 inhibitor, PLX5622, in chow, to induce microglia turnover, or control chow. In adulthood (~P80), mice received a sham procedure or a lateral fluid percussion injury. Behavioral testing was conducted from 7-14 days post injury (DPI), including elevated plus maze (EPM), Y-maze, forced swim (FST), and HPA function testing. 7DPI brains were processed to assess microgliosis and microglia engulfment of synaptic elements in the prefrontal cortex.
Results: In the EPM, ELA and TBI increased time in open arms in males. In the FST, ELA reduced active swimming time in males. In the Y-maze, TBI decreased percent spontaneous alternations in males. Corticosterone ELISA results revealed that forced microglia turnover leads to decreased corticosterone at baseline and in response to an acute stressor.
Conclusions and Future Directions: ELA programs long term mood-related behavioral changes, and TBI alters spatial working memory in males. Further work is needed to explore the underlying mechanism leading to sex differences in behavioral outcomes.
Keywords: Traumatic Brain Injury, Early Life Stress, Microglia