The<i>APOE</i>Genotype Affects Synaptic Vesicles and Myelin Sheaths in Respiratory Motor Control Regions Following a C2 Hemisection

Nearly 300,000 people in the United States are living with spinal cord injuries (SCI), and each year, approximately 17,000 more individuals sustain an injury. One aspect of SCI recovery that remains poorly understood at this time is the role of genetic factors. We chose to examine the APOE gene, which encodes for the lipid membrane transport protein apolipoprotein E and is historically associated with the development of Alzheimer’s disease. Utilizing humanized APOE targeted replacement mice homozygous for either the E3 or E4 allele, our lab has previously demonstrated that the APOE genotype impacts respiratory motor control and plasticity, making this gene an excellent target for further investigation. To elucidate the mechanisms behind these differences and examine potential targets for treatment following SCI, we explored histological markers associated with synaptic transmission and plasticity. We hypothesized that our E4 mice would have decreased markers of transmission and plasticity relative to E3 counterparts as measured via FlouroMyelin staining and synaptic vesicle marker 2 (SV2) respectively. FluoroMyelin staining revealed distinct genotype-dependent differences both under intact conditions and post-injury, highlighting significant changes in myelin levels. SV2 immunohistochemistry was quantified to assess differences in synaptic vesicles among the genotypes and sexes. Results indicate a genotype-specific influence on plasticity, with the APOE4 genotype presenting less SV2 immunoreactivity in key respiratory motor control regions in comparison to its counterpart. This demonstrates that genetic predisposition may affect future therapeutic success following cervical SCI. Further investigation using additional markers and staining in peripheral organs can contribute to a better understanding of how genetic variations influence systemic recovery mechanisms. Ultimately, our findings show that the diversity of genotypes in the clinical SCI population requires a tailored approach to treatment, emphasizing the notion that there is no "one-size-fits-all" strategy in the treatment of spinal cord injuries. Craig H. Neilsen Foundation (WJA) Kentucky Spinal Cord and Head Injury Research Trust OBE Summer Undergraduate Research Fellowship This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.