Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders

Abstract

Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

“…peroxiredoxins, another antioxidant enzyme family, are widely distributed in neuronal cells (Peshenko et al, 1998) and play a protective role against the oxidative stress component of neurodegenerative disorders by reducing cellular hydrogen peroxide (Goemaere and Knoops, 2011;Zhu et al, 2012). Others have reported a strong elevation in gst pi and prdx1 mRNA expression, and minor increases in gclc and hmox1 in response to Nrf2 activators in olfactory tissue by in situ hybridization .…”

Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells

“…Moreover, neuronal cells bear relatively weak antioxidant defense due to reduced expression of antioxidants with high levels of phospholipids, which are highly sensitive to oxidative modification (18,50). The protective activity of Prdx6 has been documented in neuronal cells (3,29). Most of the antioxidant proteins including Prdx6 reside in cytosol to remove ROS enzymatically.…”

“…Furthermore, Prdx6 is a potent cytoprotective enzyme in the epidermis (40) and is required for blood vessel integrity in wounded skin (41). Prdxs are distributed in the normal mammalian brain (29). Aon-Bertolino et al (3) reported a relatively intense Prdx6 staining in the hippocampus of the rat brain (34).…”

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

“…Aon-Bertokino et al (3) reported a relatively intense Prdx6 staining in the hippocampus of the rat brain (42). The defensive role of Prdx6 has been shown in neurodegenerative disorders (33,75,79). The physiological expression of Prdx6 appears to be critical for maintaining cellular integrity and cellular protection within the cellular microenvironment, and these qualities make it an ideal molecule for therapeutic uses.…”

“…Furthermore, Prdx6 is a potent cytoprotective enzyme in the epidermis (51) and is required for blood vessel integrity in wounded skin (52). Prdxs are distributed in the normal mammalian brain (33). Aon-Bertokino et al (3) reported a relatively intense Prdx6 staining in the hippocampus of the rat brain (42).…”