Poster abstracts
Poster number 99 submitted by Christopher Cotter
Apoe4/Trem2R47H Behavioral Phenotyping Reveals Genotype-Dependent Impairments in Spatial Memory and Associative Learning following Traumatic Brain Injury
Christopher Cotter (Institute for Behavioral Medicine Research, Department of Neuroscience), Sam Houle (Institute for Behavioral Medicine Research, Department of Neuroscience), Julie Fitzgerald (Institute for Behavioral Medicine Research, Department of Neuroscience), Zach Zimomra (Institute for Behavioral Medicine Research, Department of Neuroscience), Zoe Tapp-Poole ( Institute for Behavioral Medicine Research, Department of Neuroscience), Olga Kokoiko-Cochran (Institute for Behavioral Medicine Research, Department of Neuroscience)
Abstract:
The Apolipoprotein-ɛ4 (APOE-ɛ4) allele and the Triggering receptor Expressed on Myeloid Cells 2 (TREM2) R47H variant confer increased genetic risk for late-onset Alzheimer’s disease and are associated with poor outcome after traumatic brain injury (TBI). APOE and TREM2 work together to influence glial activity within the brain, which is critical in regulating memory and anxiety. We hypothesize that mice harboring APOE-ɛ4/TREM2R47H risk variants will have worsened behavioral deficits after TBI. We performed a lateral fluid percussion injury in APOE-ɛ4/TREM2-R47H knock-in (KI) mice while using APOE-ɛ3 KI mice as a control. Acutely after injury, APOE-ɛ4/TREM2R47H had increased locomotive activity, rearing episodes, and exploratory behavior in Open Field that was exaggerated by TBI in APOE-ɛ3 KI mice. We found no significant difference in anxiety-like behavior using the Elevated Zero maze. Using the Morris Water Maze, spatial search strategy, memory acquisition, and memory retention was impaired by TBI; however, APOE-ɛ4/TREM2R47H mice elicited a divergent impairment when compared to APOE- ɛ3 KI mice. In a Fear-Conditioning paradigm, TBI exacerbated deficits in memory acquisition for APOE-ɛ4/TREM2R47H mice. Memory retention of fear conditioning was impaired by genotype but only exacerbated by TBI in APOE-ɛ3 KI mice. This data suggests there are strong genotype-dependent effects that alter hippocampal dependent behavioral responses to TBI. While TBI exaggerates deficits in hippocampal-dependent behaviors in APOE-ɛ4/TREM2R47H mice, the presence of genetic risk factors encourages a differential response to injury.
References:
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Keywords: APOE4, Traumatic Brain Injury, Genetic Risk Factors