Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Neuron-specific Atg7 deletion confers neuroprotection in a mouse model of severe neonatal hypoxia-ischemia by preventing neuronal RCD.
“The neuron-specific deletion of Atg7 confers robust neuroprotection in a mouse model of severe neonatal hypoxia-ischemia by preventing neuronal RCD [847].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [847]
Brain-specific deletion of Atg7 confers protection against neonatal hypoxia-ischemia injury in mice.
“brain‐specific deletion of Atg7 confers protection against neonatal hypoxia–ischemia injury in mice (Koike et al, 2008; Xie et al, 2016).”
From Autophagy in major human diseases (2021) · cites this paper as Xie et al, 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Self-citationSemple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M., & Noble-Haeusslein, L. J. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.001 · Cited by 2,132 · see citing works
Self-citationRegulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcı́a-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,726 · see citing works
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
Autophagy modulation as a potential therapeutic target for diverse diseases
Rubinsztein, D. C., Codogno, P., & Levine, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3802 · Cited by 1,429 · see citing works
Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis
Yousefi, S., Perozzo, R., Schmid, I., Ziemiecki, A., Schaffner, T. J., Scapozza, L., Brunner, T., & Simon, H. (2006) · Nature Cell Biology · doi:10.1038/ncb1482 · Cited by 1,300 · see citing works
Wu, Y.-T., Tan, H.-L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C.-N., Codogno, P., & Shen, H.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.080796 · Cited by 1,127 · see citing works
Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review
Mwaniki, M. K., Atieno, M., Lawn, J. E., & Newton, C. R. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61577-8 · Cited by 860 · see citing works
Childhood Outcomes after Hypothermia for Neonatal Encephalopathy
Shankaran, S., Pappas, A., McDonald, S. A., Vohr, B. R., Hintz, S. R., Yolton, K. A., Gustafson, K. E., Leach, T. M., Green, C., Bara, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112066 · Cited by 738 · see citing works
(2014) · doi:10.1523/jneurosci · Cited by 715 · see citing works
Liu, Y., Shoji-Kawata, S., Sumpter, R. M., Wei, Y., Ginet, V., Zhang, L., Posner, B., Tran, K. A., Green, D. R., Xavier, R. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319661110 · Cited by 607 · see citing works
Self-citationCheng, Y., Deshmukh, M., D'Costa, A. P., Demaro, J. A., Gidday, J. M., Shah, A. R., Sun, Y., Jacquin, M., Johnson, E. M., & Holtzman, D. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2169 · Cited by 505 · see citing works
Self-citationInhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Death after Hypoxic-Ischemic Injury
Koike, M., Shibata, M., Tadakoshi, M., Gotoh, K., Komatsu, M., Waguri, S., Kawahara, N., Kuida, K., Nagata, S., Kominami, E., et al. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.070876 · Cited by 486 · see citing works
Self-citationVirgin, H. W., & Levine, B. (2009) · Nature Immunology · doi:10.1038/ni.1726 · Cited by 453 · see citing works
Protective role of autophagy in neonatal hypoxia–ischemia induced brain injury
Carloni, S., Buonocore, G., & Balduini, W. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.07.022 · Cited by 444 · see citing works
The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia
Zhu, C., Wang, X., Xu, F., Bahr, B. A., Shibata, M., Uchiyama, Y., Hagberg, H., & Blomgren, K. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401545 · Cited by 400 · see citing works
Self-citationNeuronal cell death in neonatal hypoxia‐ischemia
Northington, F. J., Chavez‐Valdez, R., & Martin, L. J. (2011) · Annals of Neurology · doi:10.1002/ana.22419 · Cited by 378 · see citing works
Erythropoietin Improved Neurologic Outcomes in Newborns With Hypoxic-Ischemic Encephalopathy
Zhu, C., Kang, W., Xu, F., Cheng, X., Zhang, Z., Jia, L., Ji, L., Guo, X., Xiong, H., Simbruner, G., et al. (2009) · PEDIATRICS · doi:10.1542/peds.2008-3553 · Cited by 354 · see citing works
Self-citationFriedman, L. G., Lachenmayer, M. L., Wang, J., He, L., Poulose, S. M., Komatsu, M., Holstein, G. R., & Yue, Z. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5809-11.2012 · Cited by 303 · see citing works
Zhu, C., Qiu, L., Wang, X., Hallin, U., Candé, C., Kroemer, G., Hagberg, H., & Blomgren, K. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01832.x · Cited by 288 · see citing works
Self-citationCarloni, S., Girelli, S., Scopa, C., Buonocore, G., Longini, M., & Balduini, W. (2010) · Autophagy · doi:10.4161/auto.6.3.11261 · Cited by 269 · see citing works
Postischemic treatment of neonatal cerebral ischemia should target autophagy
Puyal, J., Vaslin, A., Mottier, V., & Clarke, P. G. H. (2009) · Annals of Neurology · doi:10.1002/ana.21714 · Cited by 261 · see citing works
Self-citationSheng, R., Zhang, L., Han, R., Liu, X.-Q., Gao, B., & Qin, Z. (2010) · Autophagy · doi:10.4161/auto.6.4.11737 · Cited by 237 · see citing works
Zhu, C., Wang, X., Deinum, J., Huang, Z., Gao, J.-F., Modjtahedi, N., Neagu, M. R., Nilsson, M., Eriksson, P. S., Hagberg, H., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070193 · Cited by 224 · see citing works
Self-citationPuyal, J., Ginet, V., & Clarke, P. G. H. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.002 · Cited by 218 · see citing works
Self-citationZhu, C., Wang, X., Huang, Z., Qiu, L., Xu, F., Vahsen, N., Nilsson, M., Eriksson, P. S., Hagberg, H., Culmsee, C., et al. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402053 · Cited by 213 · see citing works
Self-citationMitochondria: hub of injury responses in the developing brain
Hagberg, H., Mallard, C. E., Rousset, C. I., & Thornton, C. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70261-8 · Cited by 194 · see citing works
Pathological apoptosis in the developing brain
Blomgren, K., Leist, M., & Groc, L. (2007) · APOPTOSIS · doi:10.1007/s10495-007-0754-4 · Cited by 181 · see citing works
Self-citationBeclin 1-independent autophagy contributes to apoptosis in cortical neurons
Grishchuk, Y., Ginet, V., Truttmann, A. C., Clarke, P. G. H., & Puyal, J. (2011) · Autophagy · doi:10.4161/auto.7.10.16608 · Cited by 179 · see citing works
Self-citationInvolvement of autophagy in hypoxic-excitotoxic neuronal death
Ginet, V., Spiehlmann, A., Rummel, C., Rudinskiy, N., Grishchuk, Y., Luthi‐Carter, R., Clarke, P. G., Truttmann, A. C., & Puyal, J. (2014) · Autophagy · doi:10.4161/auto.28264 · Cited by 159 · see citing works
Self-citationBilateral lesions of thalamus and basal ganglia: origin and outcome
Krägeloh‐Mann, I., Helber, A., Mader, I., Staudt, M., Wolff, M., Groenendaal, F., & de Vries, L. S. (2002) · Developmental Medicine & Child Neurology · doi:10.1017/s0012162201002389 · Cited by 159 · see citing works
Ginet, V., Puyal, J., Clarke, P. G. H., & Truttmann, A. C. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090463 · Cited by 152 · see citing works
Self-citationCaspase-3 Activation after Neonatal Rat Cerebral Hypoxia-Ischemia
Wang, X., Karlsson, J., Zhu, C., et al. (2001) · Neonatology · doi:10.1159/000047087 · Cited by 147 · see citing works
Self-citationLithium reduces apoptosis and autophagy after neonatal hypoxia–ischemia
Li, Q., Li, H., Roughton, K., et al. (2010) · Cell Death and Disease · doi:10.1038/cddis.2010.33 · Cited by 137 · see citing works
Self-citationDevelopmental Shift of Cyclophilin D Contribution to Hypoxic-Ischemic Brain Injury
Wang, X., Carlsson, Y., Basso, E., Zhu, C., Rousset, C. I., Rasola, A., Johansson, B. R., Blomgren, K., Mallard, C. E., Bernardi, P., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5832-08.2009 · Cited by 125 · see citing works
Self-citationBilateral lesions of thalamus and basal ganglia: origin and outcome
Krägeloh‐Mann, I., Helber, A., Mader, I., et al. (2002) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2002.tb00309.x · Cited by 116 · see citing works
ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage
Kessel, D., Price, M., & Reiners, J. J. (2012) · Autophagy · doi:10.4161/auto.20792 · Cited by 108 · see citing works
Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis
Nassif, M., Valenzuela, V., Rojas-Rivera, D., Vidal, R., Matus, S., Castillo, K., Fuentealba, Y., Kroemer, G., Levine, B., & Hetz, C. (2014) · Autophagy · doi:10.4161/auto.28784 · Cited by 100 · see citing works
Self-citationLysosome Dysfunction Triggers Atg7-dependent Neural Apoptosis*
Walls, K. C., Ghosh, A., Franklin, A. V., Klocke, B., Ballestas, M., Shacka, J., Zhang, J.-H., & Roth, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.103747 · Cited by 87 · see citing works
Targeting autophagy to prevent neonatal stroke damage
Puyal, J., & Clarke, P. G. H. (2009) · Autophagy · doi:10.4161/auto.5.7.9728 · Cited by 83 · see citing works
Self-citationGenetic inhibition of caspase‐2 reduces hypoxic‐ischemic and excitotoxic neonatal brain injury
Carlsson, Y., Schwendimann, L., Vontell, R., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22431 · Cited by 69 · see citing works
Oppenheim, R. W., Blomgren, K., Ethell, D. W., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4575-07.2008 · Cited by 34 · see citing works
Self-citationHughes, K. J., & Kennedy, B. K. (2012) · Science · doi:10.1126/science.1221365 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationKlionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationMolecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646 · see citing works
Self-citationAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585 · see citing works
Self-citationPharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842 · see citing works
Self-citationAutophagy-dependent cell death
Denton, D., & Kumar, S. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0252-y · Cited by 777 · see citing works
Autophagy-dependent cell death—where.; how and why a cell eats itself to death
Bialik, S., Dasari, S. K., & Kimchi, A. (2018) · Journal of Cell Science · doi:10.1242/jcs.215152 · Cited by 295 · see citing works
Autophagy in acute brain injury
Galluzzi, L., Bravo-San Pedro, J. M., Blomgren, K., & Kroemer, G. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.51 · Cited by 234 · see citing works
Self-citationAutophagy in neurodegeneration: New insights underpinning therapy for neurological diseases
Corti, O., Blomgren, K., Poletti, A., & Beart, P. M. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15002 · Cited by 141 · see citing works
Self-citation
- Authors
- 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.
- Affiliations
- University of Gothenburg (SE)
- University of Lausanne (CH)
- Zhengzhou Children's Hospital (CN)
- Juntendo University (JP)
- Third Affiliated Hospital of Zhengzhou University (CN)
- Zhengzhou University (CN)
- Centre Hospitalier Universitaire Vaudois (CH)
- Inserm (FR)
- Karolinska University Hospital (SE)
- Corresponding author
- Puyal, Julien
- Blomgren, Klas
- Zhu, Changlian
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-02-01
- Volume
- 12
- Issue
- 2
- Pages
- 410-423
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4835980
- OpenAlex
- W2232187600
- Cited by
- 160
- References
- 45
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 17 · 2021: 18 · 2020: 26 · 2019: 14 · 2018: 20 · 2017: 20 · 2016: 11
- FWCI
- 25.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autophagy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- IRIS (submittedVersion)
- Funders
- National Science Foundation
- Swedish Cancer Foundation
- Fondation Leducq
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (163064, 130769, 310030)
- National Natural Science Foundation of China
- Stiftelserna Wilhelm och Martina Lundgrens
- Vetenskapsrådet
- Göteborgs Läkaresällskap
- Barncancerfonden
- Université de Lausanne
- Svenska Läkaresällskapet
- Japan Society for the Promotion of Science (25460276, 15H01388, 26111519)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- ATG7, neonatal hypoxia-ischemia, perinatal asphyxia, hypoxic-ischemic encephalopathy, neuronal cell death, neuroprotection, lentiform nucleus, caspase-dependent cell death, caspase-independent cell death, autophagy inhibition, therapeutic target
- MeSH terms
- Neuroprotection, Autophagy-Related Protein 7, Animals, Animals, Newborn, Asphyxia Neonatorum, Brain Injuries, Cell Nucleus, Corpus Striatum, Enzyme Activation, Heat-Shock Proteins, Humans, Infant, Newborn, Inflammation, Mitochondria, Neurons, Gene Deletion, Integrases, Hypoxia-Ischemia, Brain, Protein Transport, Apoptosis Inducing Factor, Mice, Caspase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
