Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons.

Livia Carrascal,Ricardo Pardillo-Díaz,Patricia Perez-García,Ella Gorton,Ricardo Gómez-Oliva,Pedro Nunez-Abades,Carmen Castro

doi:10.3390/antiox9121307

Abstract

Oxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2–P7); infantile (P11–P15); and young adult (P20–P40). Oxidative stress was induced by 10 µM of cumene hydroperoxide (CH) application. In newborn rats, using the whole cell patch-clamp technique in brain slices, no significant modifications in membrane excitability were found. In infantile rats, the input resistance increased and rheobase decreased due to the blockage of GABAergic tonic conductance. Lipid peroxidation induced by CH resulted in a noticeable increase in protein-bound 4-hidroxynonenal in homogenates in only infantile and young adult rat slices. Interestingly, homogenates of newborn rat brain slices showed the highest capacity to respond to oxidative stress by dramatically increasing their glutathione and free thiol content. This increase correlated with a time-dependent increase in the glutathione reductase activity, suggesting a greater buffering capacity of newborn rats to resist oxidative stress. Furthermore, pre-treatment of the slices with glutathione monoethyl ester acted as a neuroprotector in pyramidal neurons of infantile rats. We conclude that during maturation, the vulnerability to oxidative stress in rat motor neurons increases with age.

Highlights

Oxidative stress is a pathological condition defined as the imbalance between harmful reactive oxygen species (ROS) and antioxidant defenses in an organism
A preliminary experiment was carried out to ensure that neurons could maintain their intrinsic electrophysiological properties during a minimum of 30 min of recording to be certain that any changes observed in the properties were due to the effect of cumene hydroperoxide (CH), rather than the effects of time
Our results indicate that brain cells from newborn rats increased their GSH content in response to CH, having a greater resistance to oxidative stress, which correlates with their ability to maintain their membrane electrical properties

Summary

Introduction

Oxidative stress is a pathological condition defined as the imbalance between harmful reactive oxygen species (ROS) and antioxidant defenses in an organism. The superoxide anion (O2−) is the most common ROS molecule found in the human body under physiological conditions, with the primary source of this anion being the mitochondria as a result of the leakage of electrons onto stable oxygen molecules during respiration. This anion can interact with hydrogen peroxide and nitric oxide to produce two other harmful intermediates: Peroxynitrate and the hydroxyl ion [2]. ROS have been shown to alter the electrical membrane properties of cells, including the cell membrane potential, ionic gradients, and cell excitability [10]

Objectives

Results

Conclusion