The Peroxiredoxin 6 gene plays a critical role in the homeostatic regulation of fear response

Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme implicated in redox regulation and expressed in many organs including the brain. It is known to participate in many psychiatric functions, but its role in fear memory is unknown. The present study demonstrates that PRDX6 plays a critical role in the regulation of fear response. Using Prdx6 knockout (Prdx6-/-) mice, we identified that PRDX6 acts as a suppressor in fear memory formation. Lack of Prdx6 leads to the faster fear acquisition and enhanced contextual fear response. This phenomenon was confirmed by the fact that injection of lentivirus-carried human PRDX6-V5 into the hippocampus of Prdx6-/- mice restored the enhanced fear response to the wild-type level. In the hippocampus of Prdx6-/- mice, calcium-dependent PLA2 level was increased, which may compensate for the lack of aiPLA2 function to maintain normal synaptic membranes. On the other hand, reactive oxygen species (ROS) levels did not change, indicating loss of peroxidase function did not affect the regulation of fear response.