Julian Craft
Research Mentor: Ashley Loeven
Mentor Department: Molecular and Integrative Physiology, Medicine
Author(s): Julian Craft, Ashley M. Loeven, Peter C. D. Macpherson, Susan V. Brooks
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 54
Abstract
Neuromuscular junction (NMJ) recovery after nerve injury requires axon degeneration, myelin clearance, and axon regrowth to postsynaptic muscle fibers. The NMJ is composed of three parts: the presynaptic motor neuron that releases acetylcholine, the postsynaptic muscle fiber endplate densely packed with acetylcholine receptors, and perisynaptic Schwann cells. Our lab has recently reported enhanced secreted phosphoprotein-1 (Spp1) signaling in S100+ cells isolated from denervated skeletal muscle compared to innervated controls (Guzman et al., 2025). Elevated expression of Spp1 mRNA and protein was observed in muscle after nerve crush injury, and treatment of denervated muscles with an Spp1 neutralizing antibody hindered anatomical and functional recovery of the neuromuscular junction (Guzman et al., 2025). However, the extent to which Spp1 regulates Schwann cell localization to endplates and Schwann cell proliferation after injury remains unclear. I hypothesize that global Spp1 knockout (-/-) mice will exhibit decreased Schwann cell localization to endplates and reduced Schwann cell proliferation after injury when compared to wildtype (WT) counterparts. 19-month-old mice (WT or Spp1-/-, n=2-3/group) were subject to unilateral peroneal nerve crush and tibialis anterior muscles were harvested at 7 or 14 days post injury. Immunohistochemistry was performed to visualize acetylcholine receptors (a-bungarotoxin), proliferating cells (Ki-67), and Schwann cells (S100B) in order to quantify the number of Schwann cells localized to the endplate and the number of proliferating Schwann cells. I anticipate observing reduced Schwann cell localization to the endplates and decreased proportion of proliferating Schwann cells in Spp1-/- muscle compared to WT muscle following injury. If so, this suggests that Spp1 is important for both Schwann cell localization to the endplates and Schwann cell proliferation after nerve crush injury.
