Proteomic Analysis of Deafferentation-Induced Changes in the Chick Cochlear Nucleus

A subpopulation of neurons in the chick cochlear nucleus, nucleus magnocellularis (NM), dies following cochlea removal. Previous studies using a "candidate molecule" approach, in which molecules known to regulate cell death in other systems are selectively investigated, have identified several proteins that are up- or down-regulated in NM following deafness. A problem with this approach, however, is that it will miss many potentially important candidates. The present study sought to perform a more complete profile of proteomics changes in response to deafferentation. Early post-hatch chicks were deafferented by a unilateral removal of the basilar papilla (cochlea) and sacrificed 3 hours, 6 hours, or 1 week later. Proteins from NM tissue on the deaf and intact side of the brain were analyzed using nanospray LC/MSE with a Waters Corp. Synapt G2 HS Mass Spectrometer, and data were processed in ProteinLynx Global SERVERTM. At each time point, several pro-survival proteins were found to be increased on the deafferented NM. Many of the proteins that were identified were related to managing ATP levels in neurons and have also been shown to be neuroprotective in other systems. Several more proteins are known to interact with and inhibit known apoptotic proteins. Here, we provide evidence for deafferentation-induced protein changes at three time points following deafferentation. We also name several proteins that are likely involved in the survivability of NM neurons following deafferentation.