The role of p75NTR in inducing axonal degeneration after injury

MONTROULL, LAURA; PFISTER, BRYAN; FRIEDMAN, WILMA J.

Congreso; Neurotrophic Mechanisms in Health and Disease Gordon Research Conference; 2019

Expression of p75NTR is induced in numerous Central Nervous System (CNS) neurons after damage in the adult brain and has been shown to regulate neuronal cell death in several injury models. While the neuropathological consequences of TBI are heterogeneous, diffuse axonal injury is ubiquitous at all severity levels, leading to deficits in connectivity that may or may not recover over time. p75NTR has been widely studied in the Peripheral Nervous System in various injury and cell-death paradigms, as well as in developmental axonal pruning and degeneration. However, the role of this receptor in mediating axonal degeneration in the CNS after TBI remains unclear. To determine the role of p75NTR in this process we performed in vivo and in vitro experiments. We subjected adult mice to mild traumatic injury using lateral fluid percussion brain (LFP) injury model. We found that one day after LFP, p75NTR is upregulated in axons and this increase is maintained 3 days after the injury. The colocalization of p75NTR with βAPP, suggest that those axons are degenerating. To understand the mechanisms of p75NTR in mediating axonal degeneration and to examine axon-specific signaling mechanisms, we are using an in vitro model of axonal stretch injury. Cortical neurons subjected to 45% or 60% of axonal stretch showed an increase in p75NTR expression in axons after 45min and a significative increase in the axonal fragmentation index one day after stretch injury. On the contrary, cortical neurons cultured from p75NTR-/- rats showed less axonal degeneration than neurons cultured from WT animals one day after injury suggesting the participation of this receptor in inducing axonal degeneration.