ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2019
Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- The aging choroid plexus and its relationship with gut dysbiosis and Klotho decline: possible intervention strategies.GeroScience · 2025Review
- Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.Molecular neurobiology · 2024Article
- A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice.Nature communications · 2024Article
- The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission-An Up-to-Date Review.International journal of molecular sciences · 2023Review
- Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons.Scientific reports · 2023Article
- Relationships between serum Klotho concentrations and cognitive performance among older chronic kidney disease patients with albuminuria in NHANES 2011-2014.Frontiers in endocrinology · 2023Article
- Transcriptional changes in the rat brain induced by repetitive transcranial magnetic stimulation.Frontiers in human neuroscience · 2023Article
- The Interrelated Multifactorial Actions of Cortisol and Klotho: Potential Implications in the Pathogenesis of Parkinson's Disease.Brain sciences · 2022Review
- Neuroprotective action of α-Klotho against LPS-activated glia conditioned medium in primary neuronal culture.Scientific reports · 2022Article
- Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Insulin Resistance in Peripheral Tissues and the Brain: A Tale of Two Sites.Biomedicines · 2022Review
- Functional Assessment of Stroke-Induced Regulation of miR-20a-3p and Its Role as a Neuroprotectant.Translational stroke research · 2022Article
- Association of 'Klotho' gene polymorphism with cerebral infarction.Journal of medical biochemistry · 2022Article
- Inducing Energetic Switching Using Klotho Improves Vascular Smooth Muscle Cell Phenotype.International journal of molecular sciences · 2021Article
- Endoplasmic Reticulum Interaction Supports Energy Production and Redox Homeostasis in Mitochondria Released from Astrocytes.Translational stroke research · 2021Article
- Mitochondrial quality control in acute ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Circulating α-klotho regulates metabolism via distinct central and peripheral mechanisms.Metabolism: clinical and experimental · 2021Review
- Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration.International journal of molecular sciences · 2021Article
- Effects of O-GlcNAcylation on functional mitochondrial transfer from astrocytes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction.Neuronal signaling · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknown. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of FGFR1, Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together, these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons and other cells types as a metabolic substrate.
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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.