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Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal...

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Autores principales: Xie, Cuicui, Ginet, Vanessa, Sun, Yanyan, Koike, Masato, Zhou, Kai, Li, Tao, Li, Hongfu, Li, Qian, Wang, Xiaoyang, Uchiyama, Yasuo, Truttmann, Anita C., Kroemer, Guido, Puyal, Julien, Blomgren, Klas, Zhu, Changlian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835980/
https://www.ncbi.nlm.nih.gov/pubmed/26727396
http://dx.doi.org/10.1080/15548627.2015.1132134
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author Xie, Cuicui
Ginet, Vanessa
Sun, Yanyan
Koike, Masato
Zhou, Kai
Li, Tao
Li, Hongfu
Li, Qian
Wang, Xiaoyang
Uchiyama, Yasuo
Truttmann, Anita C.
Kroemer, Guido
Puyal, Julien
Blomgren, Klas
Zhu, Changlian
author_facet Xie, Cuicui
Ginet, Vanessa
Sun, Yanyan
Koike, Masato
Zhou, Kai
Li, Tao
Li, Hongfu
Li, Qian
Wang, Xiaoyang
Uchiyama, Yasuo
Truttmann, Anita C.
Kroemer, Guido
Puyal, Julien
Blomgren, Klas
Zhu, Changlian
author_sort Xie, Cuicui
collection PubMed
description Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy.
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spelling pubmed-48359802016-04-29 Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury Xie, Cuicui Ginet, Vanessa Sun, Yanyan Koike, Masato Zhou, Kai Li, Tao Li, Hongfu Li, Qian Wang, Xiaoyang Uchiyama, Yasuo Truttmann, Anita C. Kroemer, Guido Puyal, Julien Blomgren, Klas Zhu, Changlian Autophagy Translational Research Paper Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. Taylor & Francis 2016-01-04 /pmc/articles/PMC4835980/ /pubmed/26727396 http://dx.doi.org/10.1080/15548627.2015.1132134 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Translational Research Paper
Xie, Cuicui
Ginet, Vanessa
Sun, Yanyan
Koike, Masato
Zhou, Kai
Li, Tao
Li, Hongfu
Li, Qian
Wang, Xiaoyang
Uchiyama, Yasuo
Truttmann, Anita C.
Kroemer, Guido
Puyal, Julien
Blomgren, Klas
Zhu, Changlian
Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title_full Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title_fullStr Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title_full_unstemmed Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title_short Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
title_sort neuroprotection by selective neuronal deletion of atg7 in neonatal brain injury
topic Translational Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835980/
https://www.ncbi.nlm.nih.gov/pubmed/26727396
http://dx.doi.org/10.1080/15548627.2015.1132134
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