ArticleOxidative medicine and cellular longevity2021
Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage: Involvement of AKT/FoxO3a/ATG-Mediated Autophagy.
Article in Oxidative medicine and cellular longevity, 2021. 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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20 citing papers in PubMed, 34 citations in OpenAlex.
- Dysfunction of hippocampal cells and its role in cognitive impairment.Neural regeneration research · 2026Article
- Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke.Neural regeneration research · 2026Article
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- Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.Journal of cellular and molecular medicine · 2024Article
- The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024Review
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Klotho inhibits IGF1R/PI3K/AKT signalling pathway and protects the heart from oxidative stress during ischemia/reperfusion injury.Scientific reports · 2023Article
- Integrative transcriptomic and network pharmacology analysis reveals the neuroprotective role of BYHWD through enhancing autophagy by inhibiting Ctsb in intracerebral hemorrhage mice.Chinese medicine · 2023Article
- Clinical and preclinical evaluation of miR-144-5p as a key target for major depressive disorder.CNS neuroscience & therapeutics · 2023Article
- Protein arginine methyltransferase 8 regulates ferroptosis and macrophage polarization in spinal cord injury via glial cell-derived neurotrophic factor.CNS neuroscience & therapeutics · 2023Article
- Transcriptional Modulation Reveals Physiological Responses to Temperature Adaptation inInternational journal of molecular sciences · 2023Article
- Non-Apoptotic Programmed Cell Death in Thyroid Diseases.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway.Inflammation · 2022Article
- RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma.Cell death & disease · 2022Article
- METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury.Cell death discovery · 2022Article
- Orexin-A exerts neuroprotective effect in experimental intracerebral hemorrhage by suppressing autophagyFrontiers in cellular neuroscience · 2022Article
- Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway.Molecular medicine reports · 2021Article
- Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage.Acta cirurgica brasileira · 2021Article
- Cryptotanshinone Inhibits the Growth of HCT116 Colorectal Cancer Cells Through Endoplasmic Reticulum Stress-Mediated Autophagy.Frontiers in pharmacology · 2021Article
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Spontaneous intracerebral hemorrhage (ICH) commonly causes secondary hippocampal damage and delayed cognitive impairments, but the mechanisms remain elusive. Here, we sought to identify the molecular mechanisms underlying these hemorrhagic outcomes in a rat autologous blood model of ICH. First, a significant increase in phosphatase and tensin homolog (PTEN) expression was observed in nonhemorrhagic ipsilateral hippocampus. However, systemic administration of PTEN inhibitor BPV or hippocampal injection of PTEN siRNA could prevent hippocampal neuronal injury and cognitive dysfunctions after ICH. Furthermore, we also found that ICH robustly triggered autophagic neuronal death in the ipsilateral hippocampus, but which were strongly reduced by PTEN knockdown. Notably, suppression of autophagy effectively attenuated poststroke hippocampal inflammation, neuronal damage, and cognitive decline, suggesting the beneficial effects of PTEN deletion was associated with autophagy inactivation. Specifically, PTEN antagonized the PI3K/AKT signaling and downstream effector FoxO3a phosphorylation and subsequently enhanced nuclear translocation of FoxO3a to drive proautophagy gene program, but these changes were diminished upon PTEN inhibition. More importantly, lentivirus-mediated FoxO3a overexpression apparently abrogated the antiauotphagy effect of PTEN deletion via enhancing autophagy-related gene (ATG) transcription. Collectively, these results suggest that knockdown of PTEN alleviated progressive hippocampal injury and cognitive deficits by suppression of autophagy induction involving the AKT/FoxO3a/ATG axis after ICH. Thus, this study provides a novel and promising therapeutic target for the treatment of hemorrhagic stroke.
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