ArticleMolecular psychiatry2021
Brain-specific suppression of AMPKα2 isoform impairs cognition and hippocampal LTP by PERK-mediated eIF2α phosphorylation.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- SCTR-Expressing Astrocyte-Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac-Foxc2 Epigenetic Axis in an AMPK-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular redox status is linked to olfactory alterations in cognitive decline.Redox biology · 2026Article
- Discovery and preclinical validation of a translationally optimized mitochondrial complex I modulator for Alzheimer's disease.npj drug discovery · 2026Article
- Suppression of neuronal p27 impairs cognitive function in middle-aged mice.Neurobiology of disease · 2026Article
- Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior.Molecular psychiatry · 2026Article
- Synaptic Potentiation in Hippocampus by eEF2K Inhibitor A484954.Hippocampus · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Activation of the AMPK Signaling and Brain Function: A Friend or Foe?Journal of neurochemistry · 2025Review
- Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia.Metabolism: clinical and experimental · 2025Article
- GENI as an AMPK Activator Binds α and γ Subunits and Improves the Memory Dysfunction of Alzheimer's Disease Mouse Models via Autophagy and Neuroprotection.Antioxidants (Basel, Switzerland) · 2025Article
- Neonatal maternal separation impairs cognitive function and synaptic plasticity in adult male CD-1 mice.IBRO neuroscience reports · 2024Article
- Suppression of neuronal AMPKβ2 isoform impairs recognition memory and synaptic plasticity.Neurobiology of disease · 2024Article
- Suppression of eEF2 phosphorylation alleviates synaptic failure and cognitive deficits in mouse models of Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Isoform-specific effects of neuronal inhibition of AMPK catalytic subunit on LTD impairments in a mouse model of Alzheimer's disease.Neurobiology of aging · 2024Article
- Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- The role of AMPKα subunit in Alzheimer's disease: In-depth analysis and future prospects.Heliyon · 2024Review
- Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK.Cell metabolism · 2024Article
- Article
- Activated AMPK Protects Against Chronic Cerebral Ischemia in Bilateral Carotid Artery Stenosis Mice.Cellular and molecular neurobiology · 2023Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The AMP-activated protein kinase (AMPK) is a molecular sensor to maintain energy homeostasis. The two isoforms of the AMPK catalytic subunit (AMPKα1 and α2) are both expressed in brains, but their roles in cognition are unknown. We generated conditional knockout mice in which brain AMPKα isoforms are selectively suppressed (AMPKα1/α2 cKO), and determined the isoform-specific effects in mice of either sex on cognition and synaptic plasticity. AMPKα2 cKO but not AMPKα1 cKO displayed impaired cognition and hippocampal late long-term potentiation (L-LTP). Further, AMPKα2 cKO mice exhibited decreased dendritic spine density and abnormal spine morphology in hippocampus. Electron microscope imaging demonstrated reduced postsynaptic density formation and fewer dendritic polyribosomes in hippocampi of AMPKα2 cKO mice. Biochemical studies revealed unexpected findings that repression of AMPKα2 resulted in increased phosphorylation of mRNA translational factor eIF2α and its kinase PERK. Importantly, L-LTP failure and cognitive impairments displayed in AMPKα2 cKO mice were alleviated by suppressing PERK activity pharmacologically or genetically. In summary, we demonstrate here that brain-specific suppression of AMPKα2 isoform impairs cognition and hippocampal LTP by PERK-mediated eIF2α phosphorylation, providing molecular mechanisms linking metabolism, protein synthesis, and cognition.
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