Poster abstracts
Poster number 79 submitted by Michaela Breach
Early life adversity changes the developing rat hippocampal transcriptome and increases later life exploratory behavior
Michaela R. Breach (Neuroscience Graduate Program), Ethan Goodman, Jonathan Packer (Neuroscience Graduate Program), Alejandra Zaleta-Lastra, Habib E. Akouri (Department of Psychology, The Ohio State University), Zoe M. Tapp (Neuroscience Graduate Program), Cole Vonder Haar, Olga Kokiko-Cochran, Jonathan P. Godbout (Department of Neuroscience, The Institute for Behavioral Medicine Research, The Chronic Brain Injury Program, The Ohio State University), Kathryn M. Lenz (Department of Psychology, Department of Neuroscience, The Institute for Behavioral Medicine Research, The Chronic Brain Injury Program,The Ohio State University)
Abstract:
Adverse childhood experiences (ACE) increase one’s risk for developing neuropsychiatric disorders later in life. ACEs may include psychosocial stress or physical violence, which may result in pediatric traumatic brain injury (TBI). On its own, pediatric TBI increases one’s risk for neuropsychiatric disorders and impaired sociocognitive functioning. Despite high prevalence rates of early life adversity and pediatric TBI, as well as substantial rates of co-occurrence, few rodent studies have sought to understand the consequences of pediatric TBI in the context of early life stress. Here, rats underwent maternal separation for 4hr/day from postnatal day (P)1-14 or were handled daily. Then, rats were subjected to either a lateral fluid percussion injury or isoflurane anesthesia on P15. At 7 days post injury (DPI) a subset of males (n = 3/group) was euthanized, and ipsilateral hippocampus was dissected. Pooled samples were processed for nuclei isolation, fixation, and barcoding. Single nucleus RNA sequencing was conducted on ~30,000 nuclei and Ingenuity Pathway Analyses were performed on differentially expressed genes. Remaining rats (n = 6-11/group, both sexes) underwent testing on open field behavior, spontaneous alternation, and spatial reference memory in adulthood (≥ 53 DPI). Results: Stress and Stress + TBI activated pathways associated with plasticity in excitatory and inhibitory neurons, including long-term potentiation and long-term depression. Stress and Stress + TBI treatment also activated various neuromodulator signaling pathways, including those of oxytocin, opioids, and dopamine. TBI activated plasticity-associated pathways in excitatory neurons only. In microglia, stress generally deactivated phagocytic and inflammatory pathways, and this was exacerbated by combination with TBI. Regarding behavioral analyses, stress significantly increased the number of entries into the center of the open field and tended to increase overall center time. Conclusion: Early life stress profoundly impacts the juvenile hippocampal transcriptome and later life exploratory behavior. Combination with TBI alters hippocampal cellular effects. Future work will apply knowledge obtained from these analyses to assess mediators of adversity-induced neurobehavioral dysfunction.
Keywords: early life stress, traumatic brain injury, hippocampus