Modulatory Effects of Mild Carbon Monoxide Exposure in the Developing Mouse Cochlea

Abstract

Carbon monoxide (CO) is well known as a highly toxic poison at high concentrations, yet in physiologic amounts it is an endogenous biological messenger in organs such as the internal ear and brain. In this study we tested the hypothesis that chronic very mild CO exposure at concentrations 25-ppm increases the expression of oxidative stress protecting enzymes within the cellular milieu of the developing inner ear (cochlea) of the normal CD-1 mouse. In addition we tested also the hypothesis that CO can decrease the pre-existing condition of oxidative stress in the mouse model for the human medical condition systemic lupus erythematosus by increasing two protective enzymes heme-oxygenase-1 (HO-1), and superoxide dismutase-2 (SOD-2). CD-1 and MRL/lpr mice were exposed to mild CO concentrations (25 ppm in air) from prenatal only and prenatal followed by early postnatal day 5 to postnatal day 20. The expression of cell markers specific for oxidative stress, and related neural/endothelial markers were investigated at the level of the gene products by immunohistochemistry, proteomics and mRNA expression (quantitative real time-PCR). We found that in the CD-1 and MRL/lpr mouse cochlea SOD-2 and HO-1 were upregulated. In this mouse model of autoimmune disease defense mechanism are attenuated, thus mild CO exposure is beneficial. Several genes (mRNA) and proteins detected by proteomics involved in cellular protection were upregulated in the CO exposed CD-1 mouse and the MRL/lpr mouse.

A tribute to John Edmond: His leadership role in founding the International Conference on Brain Energy Metabolism (ICBEM) meetings and key contributions to substrate metabolism in brain cells

“…Pre‐natal exposure was more damaging than post‐natal as changes persisted 20 days after the end of CO exposure (Lopez et al, 2009). More recently, these study techniques were adapted for use with mice to take advantage of mouse models for human medical conditions (Lopez et al, 2017).…”