Studying axo-glial interface in aging - “Studyingaxo-glial interface in aging” Peripheral neuropathies can result from inherited mutations, traumatic events, toxin exposures or be idiopathic, and are commonly affecting more severely older people. While the peripheral nervous system has the intrinsic capacity to regenerate, its regenerative properties decline severely during normal aging. Notably, age- associated loss of Schwann cells plasticity, the glial cells of the peripheral nervous system that support axonal regeneration and remyelination, was demonstrated in aging mouse models. However, once the aged Schwann cells go pass this delay it is unclear if the impaired remyelination result from aged Schwann cells intrinsic impairments in reengaging and remyelinating demyelinated axons. We hypothesized that aged Schwann cell remyelination capacity is impaired due to intrinsic defects in recognizing remyelination axonal signals, limiting nerve recovery, which constitute a new path of investigation in nerve repair during aging. We have developed an in-vitro system, the pseudopod assay, designed to isolate Schwann cell pseudopod formed in response to a suspension of neuronal cell membranes. This approach was proven to be effective at identifying numerous molecules and signaling pathways essential for the initial interaction between Schwann cell and axon during development. However, the molecules and potential remyelination signaling pathways present at the axon-Schwann cell interface when Schwann re-engage and remyelinate demyelinated axons are unclear, and how aging is altering those molecular events are unknown. Thus, we expand our pseudopod assay to identify molecules and pathways altered during axon-Schwann cell interaction between aged and young Schwann cells. To achieve this goal, we will (i) establish the proteomic profile of pseudopods generated by aged Schwann cells when initiating contact with demyelinated axons, and (ii) compare the proteome generated by young Schwann cells vs aged Schwann cells failing to reengage and remyelinate axons. We predict our results will create a powerful new molecular dataset for the aging and neuroscience research community to use for future investigation aiming at modulating juxtracrine axon-glia interaction in aged individuals.
