Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury.

Détails

Ressource 1Télécharger: BIB_DCC0A044B167.P001.pdf (1708.65 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_DCC0A044B167
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury.
Périodique
Autophagy
Auteur⸱e⸱s
Xie C., Ginet V., Sun Y., Koike M., Zhou K., Li T., Li H., Li Q., Wang X., Uchiyama Y., Truttmann A.C., Kroemer G., Puyal J., Blomgren K., Zhu C.
ISSN
1554-8635 (Electronic)
ISSN-L
1554-8627
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
12
Numéro
2
Pages
410-423
Langue
anglais
Résumé
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.
Pubmed
Web of science
Création de la notice
10/05/2016 13:27
Dernière modification de la notice
20/08/2019 16:01
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