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Study · Animal study (in vivo) · mouse · 2015

8 results

Exercise-mimetic AICAR transiently benefits brain function.

Guerrieri D, van Praag H

Oncotarget1 Jul 2015Cited by 48 (Europe PMC)

Summary

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.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR produced muscle pAMPK levels equivalent to running at the reported time points.

    In plain wordsIn mice, AICAR and running produced equivalent muscle pAMPK levels.

    Outcome
    No significant changeMuscle pAMPK
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Comparator
    running
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    500 mg/kg · 7 and 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    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.
    1 context sentence
    Summary · context
    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.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice, AICAR increased new dentate gyrus cell number.

    In plain wordsIn mice, AICAR increased new cells in the dentate gyrus.

    Outcome
    IncreaseNew dentate gyrus cell number
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    500 mg/kg · 7 daysAs given in this study (mouse).

    Source sentences

    Summary
    At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels.
    1 context sentence
    Summary · context
    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.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR increased BDNF protein levels.

    In plain wordsIn mice, AICAR increased brain-derived neurotrophic factor protein levels.

    Outcome
    IncreaseBDNF protein
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    500 mg/kg · 7 daysAs given in this study (mouse).

    Source sentences

    Summary
    At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels.
    1 context sentence
    Summary · context
    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.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR and running showed overlapping regulation of neuronal, mitochondrial and metabolism-related gene classes in brain tissue.

    In plain wordsIn mice, AICAR and running affected overlapping brain gene classes.

    Outcome
    Not applicableBrain gene regulation overlap
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Comparator
    running
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    500 mg/kgAs given in this study (mouse).

    Source sentences

    Summary
    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.
    1 context sentence
    Summary · context
    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.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In mice, AICAR no longer increased dentate gyrus cell proliferation after fourteen days.

    In plain wordsIn mice, AICAR no longer increased dentate gyrus cell growth after fourteen days.

    Outcome
    No significant changeDentate gyrus cell proliferation
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    500 mg/kg · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β.
    2 context sentences
    Summary · context
    Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days.
    Summary · context
    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.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR no longer increased neurotrophin levels after fourteen days.

    In plain wordsIn mice, AICAR no longer increased neurotrophin levels after fourteen days.

    Outcome
    No significant changeNeurotrophin levels
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    500 mg/kg · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β.
    2 context sentences
    Summary · context
    Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days.
    Summary · context
    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.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR increased apoptotic gene expression after fourteen days.

    In plain wordsIn mice, AICAR increased expression of genes involved in cell death.

    Outcome
    IncreaseApoptotic gene expression
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    500 mg/kg · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β.
    2 context sentences
    Summary · context
    Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days.
    Summary · context
    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.
  8. 08AnimalAnimal study (in vivo)Mechanism

    In mice, AICAR increased inflammatory interleukin-1β expression after fourteen days.

    In plain wordsIn mice, AICAR increased expression of inflammatory interleukin-1β.

    Outcome
    IncreaseInterleukin-1β expression
    Study

    mousen: not reported in source

    male C57BL/6J mice
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    500 mg/kg · 14 daysAs given in this study (mouse).

    Source sentences

    Summary
    The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β.
    2 context sentences
    Summary · context
    Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days.
    Summary · context
    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.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

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