ArticleOncotarget2015
Exercise-mimetic AICAR transiently benefits brain function.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- Targeting AMPK Networks for Male Reproductive Health: Mechanisms and Emerging Therapies.Cells · 2026Review
- Dual recombinase-mediated intersectional genetics defines the functional heterogeneity of neural stem cells in adult hippocampus.Molecular psychiatry · 2025Article
- Swimming Training Prevents Stress-Induced Spatial Memory Impairment by Reducing Neurodegenerative Changes in Hippocampus.Biochemistry research international · 2025Article
- Hippocampal Neurogenesis via Light-Intensity Running and Its Mechanism.Advances in neurobiology · 2025Review
- Survey of transcriptome analyses of hippocampal neurogenesis with focus on adult dentate gyrus stem cells.Frontiers in cell and developmental biology · 2025Review
- AMP-Activated Protein Kinase Treatment Ameliorates Chronic Restraint Stress Induced Memory Impairment in Early Adolescent Rat by Restoring Metabolite Profile and Synaptic Proteins.Neurochemical research · 2024Article
- IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency.EMBO reports · 2024Article
- Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer's disease.Journal of neuroinflammation · 2024Review
- Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.Psychiatry research · 2024Article
- Article
- Molecular mechanisms of exercise contributing to tissue regeneration.Signal transduction and targeted therapy · 2022Review
- Molecular targets of exercise mimetics and their natural activators.BMB reports · 2021Review
- Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.Molecular neurobiology · 2021Article
- Review
- Forgot to Exercise? Exercise Derived Circulating Myokines in Alzheimer's Disease: A Perspective.Frontiers in neurology · 2021Review
- Physical exercise in the prevention and treatment of Alzheimer's disease.Journal of sport and health science · 2020Review
- Endosomal-lysosomal dysfunction in metabolic diseases and Alzheimer's disease.International review of neurobiology · 2020Review
- Exercise and Hippocampal Memory Systems.Trends in cognitive sciences · 2019Review
- Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.Neuropharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.
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What OpenQuestion holds
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.