ArticleJournal of neurochemistry2015
A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice.
Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Pooled it
- The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.International journal of biological sciences · 2025Article
- AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.International journal of molecular sciences · 2024Article
- Metabolic stability of the Pallas' spadefoot Pelobates vespertinus under extreme hypoxia.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Article
- Drp1 acetylation mediated by CDK5-AMPK-GCN5L1 axis promotes cerebral ischemic injury via facilitating mitochondrial fission.Molecular medicine (Cambridge, Mass.) · 2024Article
- Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.Journal of the American Heart Association · 2024Article
- CAMKK2 is upregulated in primary human osteoarthritis and its inhibition protects against chondrocyte apoptosis.Osteoarthritis and cartilage · 2023Article
- PGC-1α Affects Epileptic Seizures by Regulating Mitochondrial Fusion in Epileptic Rats.Neurochemical research · 2023Article
- Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism.Molecular metabolism · 2022Article
- Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver.Metabolites · 2022Article
- Review
- Activation of AMPK under Hypoxia: Many Roads Leading to Rome.International journal of molecular sciences · 2020Review
- Neuroprotective Effects of Diabetes Drugs for the Treatment of Neonatal Hypoxia-Ischemia Encephalopathy.Frontiers in cellular neuroscience · 2020Review
- Heat Shock Factor 1 Is a Direct Antagonist of AMP-Activated Protein Kinase.Molecular cell · 2019Article
- Involvement of AMP-activated protein kinase in neuroinflammation and neurodegeneration in the adult and developing brain.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2019Review
- The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities.International journal of molecular sciences · 2019Article
- Hydrogen-rich saline promotes microglia M2 polarization and complement-mediated synapse loss to restore behavioral deficits following hypoxia-ischemic in neonatal mice via AMPK activation.Journal of neuroinflammation · 2019Review
- Inhibition of Calcium/Calmodulin-Dependent Protein Kinase Kinase β Is Detrimental in Hypoxia⁻Ischemia Neonatal Brain Injury.International journal of molecular sciences · 2019Article
- Quercetin protects PC-12 cells against hypoxia injury by down-regulation of miR-122.Iranian journal of basic medical sciences · 2019Article
- The long-term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high-fructose-fed adolescent rats.Physiological reports · 2019Article
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is pathological activation of the calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-AMPKα1 signalling pathway. Pharmacological inhibition of AMPK during the insult promotes neuronal survival but, conversely, inhibiting AMPK activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal HIE as prior sensitization such as exposure to bacterial infection (reported to reduce AMPK activity) produces a significant increase in injury. We show that in an in vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is a pathological activation of the CaMKKβ-AMPKα1 signalling pathway. Inhibiting AMPK during OGD promotes neuronal survival; conversely, inhibiting AMPK prior to OGD exacerbates cell death. Our data have clinical relevance as prior sensitization (e.g. exposure to bacterial infection reducing AMPK activity) increases injury. AMPK, AMP-activated protein kinase; HI, hypoxia-ischaemia; OGD, oxygen-glucose deprivation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.