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

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 (P...

Full description

Bibliographic Details
Main Authors: Livia Carrascal, Ella Gorton, Ricardo Pardillo-Díaz, Patricia Perez-García, Ricardo Gómez-Oliva, Carmen Castro, Pedro Nunez-Abades
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/9/12/1307
_version_ 1797544049478991872
author Livia Carrascal
Ella Gorton
Ricardo Pardillo-Díaz
Patricia Perez-García
Ricardo Gómez-Oliva
Carmen Castro
Pedro Nunez-Abades
author_facet Livia Carrascal
Ella Gorton
Ricardo Pardillo-Díaz
Patricia Perez-García
Ricardo Gómez-Oliva
Carmen Castro
Pedro Nunez-Abades
author_sort Livia Carrascal
collection DOAJ
description 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.
first_indexed 2024-03-10T13:54:59Z
format Article
id doaj.art-2ce9447acbb94805a98a95013caae2ec
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-10T13:54:59Z
publishDate 2020-12-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj.art-2ce9447acbb94805a98a95013caae2ec2023-11-21T01:43:23ZengMDPI AGAntioxidants2076-39212020-12-01912130710.3390/antiox9121307Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex NeuronsLivia Carrascal0Ella Gorton1Ricardo Pardillo-Díaz2Patricia Perez-García3Ricardo Gómez-Oliva4Carmen Castro5Pedro Nunez-Abades6Departament of Physiology, Pharmacy School, University of Seville, 41012 Seville, SpainDepartament of Physiology, Pharmacy School, University of Seville, 41012 Seville, SpainBiomedical Research and Innovation Institute of Cadiz (INIBICA), 11003 Cadiz, SpainDepartament of Physiology, Pharmacy School, University of Seville, 41012 Seville, SpainBiomedical Research and Innovation Institute of Cadiz (INIBICA), 11003 Cadiz, SpainBiomedical Research and Innovation Institute of Cadiz (INIBICA), 11003 Cadiz, SpainDepartament of Physiology, Pharmacy School, University of Seville, 41012 Seville, SpainOxidative 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.https://www.mdpi.com/2076-3921/9/12/1307oxidative stressmotor cortexglutathione levels in the brainpostnatal developmentmembrane excitabilityamyotrophic lateral sclerosis
spellingShingle Livia Carrascal
Ella Gorton
Ricardo Pardillo-Díaz
Patricia Perez-García
Ricardo Gómez-Oliva
Carmen Castro
Pedro Nunez-Abades
Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
Antioxidants
oxidative stress
motor cortex
glutathione levels in the brain
postnatal development
membrane excitability
amyotrophic lateral sclerosis
title Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
title_full Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
title_fullStr Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
title_full_unstemmed Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
title_short Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
title_sort age dependent vulnerability to oxidative stress of postnatal rat pyramidal motor cortex neurons
topic oxidative stress
motor cortex
glutathione levels in the brain
postnatal development
membrane excitability
amyotrophic lateral sclerosis
url https://www.mdpi.com/2076-3921/9/12/1307
work_keys_str_mv AT liviacarrascal agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT ellagorton agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT ricardopardillodiaz agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT patriciaperezgarcia agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT ricardogomezoliva agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT carmencastro agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons
AT pedronunezabades agedependentvulnerabilitytooxidativestressofpostnatalratpyramidalmotorcortexneurons