Journal
AUTOPHAGY
Volume 12, Issue 2, Pages 410-423Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1132134
Keywords
apoptosis; ATG7; autophagy; caspase; hypoxic-ischemic encephalopathy; newborn
Categories
Funding
- Swedish Research Council
- Swedish Childhood Cancer Foundation
- Swedish Cancer Foundation
- Frimurare Barnhus Foundations in Stockholm and Gothenburg
- Wilhelm and Martina Lundgren Foundation
- Edit Jacobson's Donations fund
- Gothenburg Medical Society
- Swedish Medical Society
- Department of Science and Technology
- Department of Health of Henan Province
- National Nature Science Foundation of China [31271152]
- Swiss National Science Foundation [310030-130769, 310030-163064]
- Foundation Emma Muschamp
- Faculty of Biology and Medicine (University of Lausanne)
- LeDucq Foundation
- Grants-in-Aid for Scientific Research [15H01388] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available