Reactive oxygen species modulate the differentiation of neurons in clonal cortical cultures

Abstract

Reactive oxygen species (ROS) are important regulators of intracellular signaling. We examined the expression of ROS during rat brain development and explored their role in differentiation using cortical cultures. High levels of ROS were found in newborn neurons. Neurons produced ROS, not connected with cell death, throughout embryogenesis and postnatal stages. By P20, ROS-producing cells were found only in neurogenic regions. Cells with low levels of ROS, isolated from E15 brains by FACS, differentiated into neurons, oligodendrocytes, and astrocytes in clonal cultures. Neurons produced high ROS early in culture and later differentiated into two types: large pyramidal-like neurons that fired no or only a single action potential and smaller neurons that expressed nuclear calretinin and fired repeated action potentials. Antioxidant treatment did not alter neuron number but increased the ratio of small to large neurons. These findings suggest that modulation of ROS levels influences multiple aspects of neuronal differentiation.

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

“…The present results suggest that Apocynin and 5-HD act by stimulating differentiation of mesencephalic precursors toward the DA phenotype. The results are consistent with those of previous studies, which have suggested that the redox state modulates differentiation of mesencephalic precursors (Studer et al, 2000;Rodriguez-Pallares et al, 2001Tsatmali et al, 2005), and with those of studies that have suggested that ROS levels affect the phenotype of cells in culture (Li et al, 2006;Xiao et al, 2009), including neurons (Tsatmali et al, 2006).…”

“…Therefore, the increase in the number of TH-ir neurons observed after treatment with Apo or 5-HD may be due to a decrease in ROS-induced cell death and the consequent increase in cell survival rate. However, several previous studies have shown that oxidative stress is not a major cause of apoptotic cell death in aggregates of neural progenitors unless they are challenged with stress inducers (Lee et al, 2003;Tsatmali et al, 2006). In addition, several previous studies have demonstrated that cell death of neural precursors within proliferating clusters is relatively rare compared with that of dissociated cells (Studer et al, 1998).…”

“…Neural precursor cells must possess the capacity to respond to multiple cues that control their fate, and ROS have been suggested as important signal mediators involved in this capacity (Limoli et al, 2004;Tsatmali et al, 2006;Sharma et al, 2008). ROS take part in the signal transduction pathways of several growth and trophic factors, cytokines and G-proteincoupled receptors (Bartosz, 2009) and regulate proliferation, differentiation, migration and apoptosis in a wide variety of cells (Sauer et al, 2001;Bedard and Krause, 2007;Dumollard et al, 2007).…”

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

“…ROS production has mainly been related to cell growth, 23 with only a few reports addressing their involvement in the triggering of specific differentiation programmes being available. 6,7,24 Although ROS production in response to haematopoietic cytokines has long been known, 10 little is known about their possible involvement in haematopoiesis. Accordingly, we were therefore prompted to study this issue in depth using megakaryocytic differentiation as a system.…”

“…4 A few recent reports have described the relevance of NADPH oxidase ROS production in the differentiation of different kind of cells. 6,7 Therefore, it is tempting to speculate that NADPH ROS production might be a general mechanism common to all types of cell differentiation. However, to confirm this, further studies should be carried out on other types of cell differentiation.…”