Spinal cord neurons and microglia post traumatic injury in SARM1-/-mice

Abstract

The sterile alpha and TIR motif containing 1 (Sarm1) gene encodes SARM1, a “Toll-like receptor adaptor protein” (Estera et al., 2021). SARM1, a catalyst for neuronal death, has been identified as a potential therapeutic target for neurodegeneration. Peripheral nerve injury causes an extensive immune response in the spinal cord. This is partly because the axons that form the sciatic nerve also comprise the dorsal column of the spinal cord. It is also possible that microglia are responding to neurodegenerative diseases that begin in the peripheral nervous system, like amyotrophic lateral sclerosis (ALS). Activation of the resident microglia in the spinal cord largely governs the immune response that is generated. SARM1’s effects have been studied more extensively in the brain than in the spinal cord, but because both the brain and the spinal cord comprise the central nervous system, it is essential to study both parts so that a more complete representation of SARM1 can be ascertained. It was asked whether the loss of Sarm1 protects or compromises the microenvironment of the spinal cord through microglia-neuronal interactions following peripheral injury. To investigate this problem, spinal cord cross sections were immunostained at 3 days, 7 days, and 14 days post sciatic nerve crush. Numerical and morphological differences in neuronal and microglial populations were assessed between Sarm1 knockout and wildtype mice. It was found that Sarm1 knockout, compared to WT, had more neurons at 3 days and 7 days and nearly identical neuronal counts at 14 days. Further, Sarm1 knockout also had greater microglial activation at 14 days. These results suggest that the loss of Sarm1 might be protective from injury-induced cell death.