ArticleJCI insight2021
Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- The Case for Vinegar Ingestion.Nutrients · 2026Review
- Article
- Dual-modal metabolic analysis reveals hypothermia-reversible uncoupling of oxidative phosphorylation in neonatal brain hypoxia-ischemia.bioRxiv : the preprint server for biology · 2025Article
- Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.Nature communications · 2025Article
- Brain energy metabolism: A roadmap for future research.Journal of neurochemistry · 2024Review
- Dodecyl creatine ester therapy: from promise to reality.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Cell-specific vulnerability to metabolic failure: the crucial role of parvalbumin expressing neurons in creatine transporter deficiency.Acta neuropathologica communications · 2023Article
- (Phospho)creatine: the reserve and merry-go-round of brain energetics.Neural regeneration research · 2023Article
- Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages.Frontiers in immunology · 2023Article
- Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
The creatine transporter (CrT) maintains brain creatine (Cr) levels, but the effects of its deficiency on energetics adaptation under stress remain unclear. There are also no effective treatments for CrT deficiency, the second most common cause of X-linked intellectual disabilities. Herein, we examined the consequences of CrT deficiency in brain energetics and stress-adaptation responses plus the effects of intranasal Cr supplementation. We found that CrT-deficient (CrT-/y) mice harbored dendritic spine and synaptic dysgenesis. Nurtured newborn CrT-/y mice maintained baseline brain ATP levels, with a trend toward signaling imbalance between the p-AMPK/autophagy and mTOR pathways. Starvation elevated the signaling imbalance and reduced brain ATP levels in P3 CrT-/y mice. Similarly, CrT-/y neurons and P10 CrT-/y mice showed an imbalance between autophagy and mTOR signaling pathways and greater susceptibility to cerebral hypoxia-ischemia and ischemic insults. Notably, intranasal administration of Cr after cerebral ischemia increased the brain Cr/N-acetylaspartate ratio, partially averted the signaling imbalance, and reduced infarct size more potently than intraperitoneal Cr injection. These findings suggest important functions for CrT and Cr in preserving the homeostasis of brain energetics in stress conditions. Moreover, intranasal Cr supplementation may be an effective treatment for congenital CrT deficiency and acute brain injury.
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Registered trials
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