Motoneuronal death during spinal cord development is mediated by oxidative stress

Abstract

The involvement of reactive oxygen species (ROS) in neuronal death has been determined in culture, and in association with several neurodegenerative disorders. We examined whether ROS participate in the cell death observed during spinal cord development. We found that the general pattern of high ROS levels, gene expression for some antioxidant enzymes, and motoneuron death correlated positively along spinal cord development. ROS were reduced in spinal cords cultured in the presence of a synthetic superoxide dismutase and catalase mimetic, with a concomitant reduction in cell death and an increase in the number of motoneurons. The number of motoneurons was higher in spinal cords treated with the antioxidant than in those treated with caspase inhibitors. In general, the increase in motoneuron survival did not correlate with the reduction in cells undergoing DNA degradation in the motoneuronal region. These results suggest that ROS are signaling molecules controlling caspase-dependent and caspaseindependent programmed motoneuron death, and support the hypothesis that this mechanism is abnormally turned on in some neurodegenerative disorders and aging.

CLP1 links tRNA metabolism to progressive motor-neuron loss

“…7a,b). Motor neuron numbers also declined in wild type embryos due to pruning, which has been linked to oxidative stress exposure 13 . NeuN staining to detect all neurons showed that the observed reduction in neuronal numbers was due to the loss of ChAT + motor neurons (Supplementary Fig.…”

Characterization of early pathogenesis in the SOD1G93A mouse model of ALS: part I, background and methods

“…These include mitochondria, the Golgi apparatus, rough endoplasmic reticulum, neuromuscular synapses, MN axons. The neuron's response to oxidative stress, ER stress, or alterations in proteasome function may manifest in these pathological changes (Sánchez-Carbente et al 2005; Fischer and Glass 2007; Boillée and Cleveland 2008; Cheroni et al 2009). Physiological changes such as alterations in anterograde and retrograde axonal transport and hyperexcitotoxicity are also reported to occur.…”

Exogenous Hsc70, but not thermal preconditioning, confers protection to motoneurons subjected to oxidative stress

“…ROS can accumulate in response to programmed cell death, injury, excitotoxicity, glucose deprivation, and neurodegenerative diseases including Spinal Muscular Atrophy (SMA), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD). (Andrus et al, 1998;Hayashi et al, 2002;Liu et al, 2003;Rego and Oliveira, 2003;Bruijn et al, 2004;Parihar and Hemnani, 2004;Zhang et al, 2004;Sanchez-Carbente et al, 2005;Xu et al, 2005;Pasinelli and Brown, 2006). These ROS, including superoxide, peroxinitrite, and hydroxyl radical exert their effects through the oxidative modification of lipid, protein, and DNA (Sayre et al, 2001).…”