Effect of 15-PGDH inhibition on skeletal muscle after sciatic nerve transection by single nuclei analysis

There are currently no approved treatments for the weakness and paralysis that result from loss of peripheral nerve function with aging, trauma, or neuromuscular disease. Here we use single nuclei sequencing to show that denervation due to transection of the sciatic nerve triggers a striking increase in the prostaglandin degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle. Sciatic nerve on one leg of a C57BL6 mouse was surgically ressected, then mice were either treated with IP injection of a 15-PGDH inhibitor daily or vehicle. Single nuclei analysis was performed on skeletal muscle of contralateral (innervated) or the SNT (denervated) legs.