Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons

Fungicides often cause genotoxic stress and neurodevelopmental disorders such as autism (ASD). Fungicide-azoxystrobin (AZOX) showed acute and chronic toxicity to various organisms, and remained a concern for ill effects in developing neurons. We evaluated the neurotoxicity of AZOX in developing mous...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jieun Kang, Kausik Bishayee, Sung-Oh Huh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	azoxystrobin neurotoxicity <i>in utero</i> electroporation primary cortical neuron mTORC1 activity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/322bc1cdce2747ff8e703c1298891fc1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:322bc1cdce2747ff8e703c1298891fc1
record_format	dspace
spelling	oai:doaj.org-article:322bc1cdce2747ff8e703c1298891fc12021-11-25T17:57:15ZAzoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons10.3390/ijms2222124951422-00671661-6596https://doaj.org/article/322bc1cdce2747ff8e703c1298891fc12021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12495https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Fungicides often cause genotoxic stress and neurodevelopmental disorders such as autism (ASD). Fungicide-azoxystrobin (AZOX) showed acute and chronic toxicity to various organisms, and remained a concern for ill effects in developing neurons. We evaluated the neurotoxicity of AZOX in developing mouse brains, and observed prenatal exposure to AZOX reduced neuronal viability, neurite outgrowth, and cortical migration process in developing brains. The 50% inhibitory concentration (IC50) of AZOX for acute (24 h) and chronic (7 days) exposures were 30 and 10 μM, respectively. Loss in viability was due to the accumulation of reactive oxygen species (ROS), and inhibited neurite outgrowth was due to the deactivation of mTORC1 kinase activity. Pretreatment with ROS scavenger- N-acetylcysteine (NAC) reserved the viability loss and forced activation of mTORC1 kinase revived the neurite outgrowth in AZOX treated neurons. Intra-amniotic injection of AZOX coupled with <i>in utero</i> electroporation of GFP-labelled plasmid in E15.5 mouse was performed and 20 mg/kg AZOX inhibited radial neuronal migration. Moreover, the accumulation of mitochondria was significantly reduced in AZOX treated primary neurons, indicative of mitochondrial deactivation and induction of apoptosis, which was quantified by Bcl2/Bax ratio and caspase 3 cleavage assay. This study elucidated the neurotoxicity of AZOX and explained the possible cure from it.Jieun KangKausik BishayeeSung-Oh HuhMDPI AGarticleazoxystrobinneurotoxicity<i>in utero</i> electroporationprimary cortical neuronmTORC1 activityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12495, p 12495 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	azoxystrobin neurotoxicity <i>in utero</i> electroporation primary cortical neuron mTORC1 activity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	azoxystrobin neurotoxicity <i>in utero</i> electroporation primary cortical neuron mTORC1 activity Biology (General) QH301-705.5 Chemistry QD1-999 Jieun Kang Kausik Bishayee Sung-Oh Huh Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
description	Fungicides often cause genotoxic stress and neurodevelopmental disorders such as autism (ASD). Fungicide-azoxystrobin (AZOX) showed acute and chronic toxicity to various organisms, and remained a concern for ill effects in developing neurons. We evaluated the neurotoxicity of AZOX in developing mouse brains, and observed prenatal exposure to AZOX reduced neuronal viability, neurite outgrowth, and cortical migration process in developing brains. The 50% inhibitory concentration (IC50) of AZOX for acute (24 h) and chronic (7 days) exposures were 30 and 10 μM, respectively. Loss in viability was due to the accumulation of reactive oxygen species (ROS), and inhibited neurite outgrowth was due to the deactivation of mTORC1 kinase activity. Pretreatment with ROS scavenger- N-acetylcysteine (NAC) reserved the viability loss and forced activation of mTORC1 kinase revived the neurite outgrowth in AZOX treated neurons. Intra-amniotic injection of AZOX coupled with <i>in utero</i> electroporation of GFP-labelled plasmid in E15.5 mouse was performed and 20 mg/kg AZOX inhibited radial neuronal migration. Moreover, the accumulation of mitochondria was significantly reduced in AZOX treated primary neurons, indicative of mitochondrial deactivation and induction of apoptosis, which was quantified by Bcl2/Bax ratio and caspase 3 cleavage assay. This study elucidated the neurotoxicity of AZOX and explained the possible cure from it.
format	article
author	Jieun Kang Kausik Bishayee Sung-Oh Huh
author_facet	Jieun Kang Kausik Bishayee Sung-Oh Huh
author_sort	Jieun Kang
title	Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
title_short	Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
title_full	Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
title_fullStr	Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
title_full_unstemmed	Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons
title_sort	azoxystrobin impairs neuronal migration and induces ros dependent apoptosis in cortical neurons
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/322bc1cdce2747ff8e703c1298891fc1
work_keys_str_mv	AT jieunkang azoxystrobinimpairsneuronalmigrationandinducesrosdependentapoptosisincorticalneurons AT kausikbishayee azoxystrobinimpairsneuronalmigrationandinducesrosdependentapoptosisincorticalneurons AT sungohhuh azoxystrobinimpairsneuronalmigrationandinducesrosdependentapoptosisincorticalneurons
_version_	1718411792975134720

Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons

Ejemplares similares