ArticleBiochimica et biophysica acta2015
Ischemia-induced autophagy contributes to neurodegeneration in cerebellar Purkinje cells in the developing rat brain and in primary cortical neurons in vitro.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Skimmianine Pretreatment Attenuates Cerebellar Neuroinflammation and Myelin Injury Following Experimental Cerebral Ischemia-Reperfusion.Antioxidants (Basel, Switzerland) · 2026Article
- Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Role of autophagy in neurotoxic protein's clearance following post-ischemic stroke: where we are and what we know?Molecular brain · 2025Review
- Differential Protective Effects of Edaravone in Cerebellar and Hippocampal Ischemic Injury Models.Cerebellum (London, England) · 2025Article
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
- Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome.Neural regeneration research · 2023Review
- Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway.Neural regeneration research · 2022Article
- Early Thalamic Injury After Resuscitation From Severe Asphyxial Cardiac Arrest in Developing Rats.Frontiers in cell and developmental biology · 2021Article
- Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.Cellular and molecular life sciences : CMLS · 2020Article
- Relative Resilience of Cerebellar Purkinje Cells in a Cardiac Arrest/Resuscitation Rat Model.Neurocritical care · 2020Article
- The role of autophagy in acute brain injury: A state of flux?Neurobiology of disease · 2019Review
- Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway.Oxidative medicine and cellular longevity · 2019Article
- Mesenchymal Stem Cells Protect Against Hypoxia-Ischemia Brain Damage by Enhancing Autophagy Through Brain Derived Neurotrophic Factor/Mammalin Target of Rapamycin Signaling Pathway.Stem cells (Dayton, Ohio) · 2018Article
- Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease.Frontiers in neuroscience · 2018Review
- Chronic inflammation and apoptosis propagate in ischemic cerebellum and heart of non-human primates.Oncotarget · 2017Article
- Time-Dependent Changes in Apoptosis Upon Autophagy Inhibition in Astrocytes Exposed to Oxygen and Glucose Deprivation.Cellular and molecular neurobiology · 2017Article
- The Brain after Cardiac Arrest.Seminars in neurology · 2017Review
- Diffusion Tensor Imaging Detects Occult Cerebellar Injury in Severe Neonatal Hypoxic-Ischemic Encephalopathy.Developmental neuroscience · 2017Article
- Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia.Neuroscience · 2016Article
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Authors and funding
11 authors at 3 institutions in 1 country.
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Abstract
Increased autophagy/mitophagy is thought to contribute to cerebellar dysfunction in Purkinje cell degeneration mice. Intriguingly, cerebellar Purkinje cells are highly vulnerable to hypoxia-ischemia (HI), related at least in part to their high metabolic activity. Whether or not excessive or supraphysiologic autophagy plays a role in Purkinje cell susceptibility to HI is unknown. Accordingly, we evaluated the role of autophagy in the cerebellum after global ischemia produced by asphyxial cardiac arrest in postnatal day (PND) 16-18 rats, using siRNA-targeted inhibition of Atg7, necessary for microtubule-associated protein light chain 3-II (LC3-II) and Atg12-Atg5 complex formation. Two days before a 9min asphyxial cardiac arrest or sham surgery, Atg7 or control siRNA was injected intracisternally to target the cerebellum. Treatment with Atg7 siRNA: 1) reduced Atg7 protein expression in the cerebellum by 56%; 2) prevented the typical ischemia-induced formation of LC3-II in the cerebellum 24h after asphyxial cardiac arrest; 3) improved performance on the beam-balance apparatus on days 1-5; and 4) increased calbindin-labeled Purkinje cell survival assessed on day 14. Improved Purkinje cell survival was more consistent in female vs. male rats, and improved beam-balance performance was only seen in female rats. Similar responses to Atg7 siRNA i.e. reduced autophagy and neurodegeneration vs. control siRNA were seen when exposing sex-segregated green fluorescent protein-LC3 tagged mouse primary cortical neurons to oxygen glucose deprivation in vitro. Thus, inhibition of autophagy after global ischemia in PND 16-18 rats leads to increased survival of Purkinje cells and improved motor performance in a sex-dependent manner.
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