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Study · Animal study (in vivo) · mouse · 2025

6 results

AMPK activation improves depression-like symptoms in olfactory bulbectomized mice by regulating microglia M1/M2 polarization in the hippocampus.

Odaira-Satoh T, Nakagawasai O, Takahashi K, Shimada M, Nemoto W, Tan-No K

Brain, behavior, & immunity - health11 May 2025Cited by 4 (Europe PMC)

PMID40491455 (opens in a new tab)PMCIDPMC12148637 (opens in a new tab)DOI10.1016/j.bbih.2025.101008 (opens in a new tab)PepBankPUB-40491455
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Summary

Several studies have reported that the activation of adenosine monophosphate-activated protein kinase (AMPK) in the central nervous system is involved in antidepressant-like effects. We recently demonstrated that AMPK activators like 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleotide (AICAR) and liver hydrolysate containing an AMPK active ingredient can prevent depression-like behaviors in animal models of depression through enhanced cell proliferation in the hippocampal dentate gyrus (DG). However, it remains unclear whether microglia are involved in the antidepressant effects of AICAR in olfactory bulbectomized (OBX) mice, which is a useful animal model of depression. Therefore, in this study, we aimed to determine the mechanism of action of AICAR in OBX mice through various behavioral tests and immunohistochemical test. OBX mice exhibited depression-like behaviors in the tail suspension test (TST), forced swimming test (FST), sucrose splash test (SST), and sucrose preference test (SPT). Immunohistochemical studies revealed decreased hippocampal neuronal cell survival and an imbalance in microglial M1/M2 polarization: increased M1-like phenotype and decreased M2-like phenotype. However, AICAR treatment for 3 weeks improved the OBX-induced prolonged immobility in the TST and FST and decreased grooming time and sucrose intake rate in the SST and SPT, respectively. Chronic AICAR administration also ameliorated the reduction in hippocampal neuronal cell survival and the imbalance in microglia polarization. Our results indicate that activated AMPK improves depression-like behavior by neuroprotection via the regulation of microglial polarity. Thus, AMPK activation offers potential therapeutic avenues for developing novel treatment strategies for neuropsychiatric disorders such as depression.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In OBX mice, AICAR improved prolonged immobility in the tail suspension test.

    In plain wordsIn mice with removed olfactory bulbs, AICAR reduced prolonged immobility compared with the OBX condition.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseTail suspension immobility
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    However, AICAR treatment for 3 weeks improved the OBX-induced prolonged immobility in the TST and FST and decreased grooming time and sucrose intake rate in the SST and SPT, respectively.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In OBX mice, AICAR improved prolonged immobility in the forced swimming test.

    In plain wordsIn mice with removed olfactory bulbs, AICAR reduced prolonged swimming-test immobility compared with the OBX condition.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseForced swimming immobility
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    However, AICAR treatment for 3 weeks improved the OBX-induced prolonged immobility in the TST and FST and decreased grooming time and sucrose intake rate in the SST and SPT, respectively.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In OBX mice, AICAR improved the grooming-time abnormality, but the sentence does not unambiguously state the direction of change.

    In plain wordsIn mice with removed olfactory bulbs, AICAR improved abnormal grooming time, but the abstract's wording leaves the direction unclear.

    Peptide
    AICAR (acadesine)
    Outcome
    Direction not reportedGrooming time
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    However, AICAR treatment for 3 weeks improved the OBX-induced prolonged immobility in the TST and FST and decreased grooming time and sucrose intake rate in the SST and SPT, respectively.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In OBX mice, AICAR improved the sucrose-intake abnormality, but the sentence does not unambiguously state the direction of change.

    In plain wordsIn mice with removed olfactory bulbs, AICAR improved abnormal sucrose intake, but the abstract's wording leaves the direction unclear.

    Peptide
    AICAR (acadesine)
    Outcome
    Direction not reportedSucrose intake rate
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    However, AICAR treatment for 3 weeks improved the OBX-induced prolonged immobility in the TST and FST and decreased grooming time and sucrose intake rate in the SST and SPT, respectively.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In OBX mice, chronic AICAR ameliorated reduced hippocampal neuronal survival.

    In plain wordsIn mice with removed olfactory bulbs, AICAR improved brain nerve-cell survival compared with the OBX condition.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseHippocampal neuronal survival
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Chronic AICAR administration also ameliorated the reduction in hippocampal neuronal cell survival and the imbalance in microglia polarization.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In OBX mice, chronic AICAR ameliorated the imbalance in microglial polarization.

    In plain wordsIn mice with removed olfactory bulbs, AICAR reduced brain immune-cell imbalance compared with the OBX condition.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseMicroglial polarization imbalance
    Study

    mousen: not reported in source

    Olfactory bulbectomized mice
    Comparator
    OBX without AICAR
    Outcome group
    Immune response · Nervous system and cognition
    Studied dose
    Dose not stated · 3 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Chronic AICAR administration also ameliorated the reduction in hippocampal neuronal cell survival and the imbalance in microglia polarization.
    1 context sentence
    Summary · context
    Immunohistochemical studies revealed decreased hippocampal neuronal cell survival and an imbalance in microglial M1/M2 polarization: increased M1-like phenotype and decreased M2-like phenotype.

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

Subjects

Terms as the source lists them.

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