Space radiation‐induced alterations in the hippocampal ubiquitin‐proteome system

Abstract

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus‐dependent cognitive tasks, including spatial memory. However, there is considerable inter‐individual susceptibility to develop SR‐induced spatial memory impairment. In this study, a robust label‐free mass spectrometry (MS)‐based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n48Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti‐exposed rats, (3) Ti‐exposed rats that had shamlike spatial memory performance, and (4) Ti‐exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti‐exposed rats. We explored the possibility that the loss of the Sham‐only proteins may arise as a result of SR‐induced changes in protein homeostasis. SR‐exposure was associated with a switch towards increased pro‐ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin‐proteome system as a determinant of SR‐induced neurocognitive deficits needs to be more thoroughly investigated.