The Role of EGFR and the P75NTR in Nerve Regeneration in a Mouse Model of Nerve Injury

Abstract

Peripheral nerve injury remains a problematic clinical issue due to poor functional recovery. This is a result of the duration of denervation greatly decreasing the probability of distal target reinnervation. Therefore, increasing the rate of axon regeneration could yield improve functional recovery following peripheral nerve injury. The goal of this thesis is first to establish a mouse median nerve injury model to provide baseline values of motor and sensory neuron pools, myelin parameters and forelimb grip strength. The nerve injury model will then be implemented in studying the roles of the epidermal growth factor receptor and the p75 neurotrophin receptor in peripheral nerve regeneration. Using this model, inhibiting epidermal growth factor receptor using gefitinib significantly increased the number of sensory neuron regeneration but resulted in hypomyelination. Moreover, mice treated with gefitinib displayed significant increase in functional recovery. Secondly, mice mutant for the p75 neurotrophin receptor were implemented in our model. These mice exhibited a decrease in sensory neuron regeneration but did not affect motor neuron regeneration, remyelination or function outcome. In summary, this thesis produced a new model to study peripheral nerve injury that provide several metrics for analysis. Using this model, the regulatory roles of the epidermal growth factor receptor and the p75 neurotrophin receptor in nerve regulation are established.