Abstract
Spinal cord injury (SCI) is a devastating form of neurotrauma. Patients who carry one or two apolipoprotein E (ApoE)4 alleles show worse functional outcomes and longer hospital stays after SCI, but the cellular and molecular underpinnings for this genetic link remain poorly understood. Thus, there is a great need to generate animal models to accurately replicate the genetic determinants of outcomes after SCI to spur development of treatments that improve physical function. Here, we examined outcomes after a moderate contusion SCI of transgenic mice expressing human ApoE3 or ApoE4. ApoE4 mice have worse locomotor function and coordination after SCI. Histological examination revealed greater glial staining in ApoE4 mice after SCI associated with reduced levels of neuronal sprouting markers. Bulk RNA sequencing revealed that subcellular processes (SCPs), such as extracellular matrix organization and inflammatory responses, were highly ranked among upregulated genes at 7 days after SCI in ApoE4 variants. Conversely, SCPs related to neuronal action potential and neuron projection development were increased in ApoE3 mice at 21 days. In summary, our results reveal a clinically relevant SCI mouse model that recapitulates the influence of ApoE genotypes on post SCI function in individuals who carry these alleles and suggest that the mechanisms underlying worse recovery for ApoE4 animals involve glial activation and loss of sprouting and synaptic activity.
Highlights
Spinal cord injury (SCI), one of the most devastating forms of neurotrauma, results in lifelong disabilities and loss of independence
To better understand the biology associated with these sets of Differentially expressed genes (DEGs), we identified subcellular processes (SCPs) represented by DEGs that were upregulated in spinal cord tissue from ApoE4 and ApoE3 SCI mice at 7 and 21 dpi and listed these by rank based on adjusted p-values (Figures 5C–F)
The present study explored the role of natural variations of the gene that encodes for human apolipoprotein E (ApoE) in determining functional recovery in an animal model after SCI
Summary
Spinal cord injury (SCI), one of the most devastating forms of neurotrauma, results in lifelong disabilities and loss of independence. ApoE Variants Modulate SCI Recovery and sensory neurons that emerge below the injury resulting in paralysis, loss of sensation, and dysregulation of the autonomic nervous system (Lang et al, 2015). Additional knowledge with regard to the cellular and molecular mechanisms that determine functional recovery is essential to stimulate further research to develop and test interventions that will improve function after SCI. The understanding of genetic factors that may influence outcomes after SCI, such as the ability to walk, grasp, or lift, is profoundly under investigated but may provide new insights with regard to the cellular and molecular determinants of outcomes after SCI that determine functional recovery. In the central nervous system (CNS), ApoE is mainly synthesized in and secreted by astrocytes, and evidence from human studies and animal models is consistent with the notion that ApoE is a key determinant of the response to different types of CNS injuries (Poirier, 1994; Teasdale et al, 1997)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
