Implication of the thioredoxin/peroxiredoxin system in spinal cord development

Due, in part, to its elevated metabolism, the central nervous system (CNS) is exposed to considerable oxidative stress deriving from endogenously produced reactive oxygen and nitrogen species (ROS/RNS). Though these toxic molecules can react with different cellular components and lead to cell damage and death, numerous studies also highlight these compounds as essential actors in redox signaling cascades. This dual role of ROS/RNS requires finely tuned regulation of cellular concentrations of these species which is accomplished by antioxidant systems. Peroxiredoxins (Prdxs), a family of thiol-dependent peroxidases, and their main reductants, thioredoxins (Trxs), represent one of the major enzymatic antioxidant systems in animal cells. In addition to their cytoprotective role, Trxs and Prdxs have been shown to modulate cellular processes, either via direct interactions or indirectly through their ability to reduce ROS/RNS. In particular, over the past few years, growing evidence has underlined the role of ROS/RNS and antioxidant enzymes in CNS development. In order to study the potential involvement of Trxs and Prdxs in processes taking place during spinal cord development, the expression of these enzymes at different stages of murine embryonic development was studied. Several striking patterns were uncovered including intense immunoreactivity of Trxs and Prdxs, in particular mitochondrial enzymes Prdx3, Prdx5 and Trx2, in spinal cord motor neurons. Thereafter, with focus on Trx2, the biological meaning of these patterns was investigated using the in ovo electroporation technique to overexpress and silence Trx2 during chick spinal cord embryonic development. Interestingly, increased motor neuronal expression of Trx2 in both the mouse and chick embryo coincided with stages at which these cells undergo developmental programmed cell death (PCD). Trx2 gain and loss of function in the spinal cord of chick embryo at this stage and in a cultured explant model of neuron PCD highlighted alterations in the number of dying neurons suggesting an implication of Trx2 in this process. The final part of this work stemmed from the apparent absence of Prdx5 in chicken tissue. Indeed, converging experimental and in silico data support the disappearance of Prdx5 in birds though it is conserved in non-avian amniotes. This observation and discussion as to the reasons behind this loss could provide insight as to the role of Prdx5 in other species and further highlights this enzyme as a particular Prdx.