UC San Diego

Schwann cells (SCs) are known for maintaining axonal integrity and promoting regeneration of injured axons in the peripheral nervous system (PNS). Studies have investigated different SC components that contribute to normal SC functionality. Low-density lipoprotein receptor-related protein-1, LRP1, is a transmembrane protein that regulates SC phenotypic modulation and is vital to SC survival. Mitochondria, the powerhouses of the cell, are crucial for ATP production and regulation of inflammatory responses, especially in SCs. Mitochondrial function and LRP1 have been linked in hepatocytes, but it is not known how LRP1 modulates SC mitochondria. To investigate the relationship between LRP1 and SC mitochondria, we utilized Transmission Electron Microscopy (TEM) on sciatic nerves of mice containing a conditional knockout of scLRP1 (scLRP1-/-) and their floxed LRP1 littermates (scLRP1+/+). In adult scLRP1-/- mice, we observed an increase in mitochondrial number in myelinated SCs and the axoplasm of associated axons compared to that of scLRP1+/+ mice. When we separated the data by sex, our findings were consistent in male scLRP1-/- mice, yet female scLRP1-/- mice demonstrated no difference in mitochondrial number in myelinated fiber axoplasm. However, in non-myelinated SCs, a decrease in SC mitochondria number was observed in female scLRP1-/- mice. An aging analysis revealed decreased mitochondrial numbers in myelinated SCs of aged scLRP1+/+ mice, however, loss of LRP1 increased mitochondrial numbers, similar to adults. Together, we hypothesize that LRP1 regulates mitochondria in myelinated and non-myelinated SCs. Other factors, such as sex and age, influence the number of SC and axoplasm mitochondria present in peripheral nerves.