AMPK-autophagy-mediated inhibition of microRNA-30a-5p alleviates morphine tolerance via SOCS3-dependent neuroinflammation suppression.

Wan L, Jia RM, Ji LL, Qin XM, Hu L, Hu F, Han Y, Pan YB, Jiang CY, Liu WT

Journal of neuroinflammation29 Jan 2022Cited by 30 (Europe PMC)

PMID35093117PMCIDPMC8800317DOI10.1186/s12974-022-02384-3PepBankPUB-35093117

Summary

BackgroundThe development of morphine tolerance is a clinical challenge for managing severe pain. Studies have shown that neuroinflammation is a critical aspect for the development of analgesic tolerance. We found that AMPK-autophagy activation could suppress neuroinflammation and improve morphine tolerance via the upregulation of suppressor of cytokine signaling 3 (SOCS3) by inhibiting the processing and maturation of microRNA-30a-5p.MethodsCD-1 mice were utilized for the tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3. Proinflammatory cytokines were measured by western blotting and real-time PCR. The levels of SOCS3 and miRNA-processing enzymes were evaluated by western blotting, real-time PCR and immunofluorescence staining.ResultsBased on experimental verification, miRNA-30a-5p could negatively regulate SOCS3. The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p. We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy. Furthermore, a miRNA-30a-5p inhibitor significantly improved morphine tolerance via upregulation of SCOS3 in mice. It markedly increased the level of SOCS3 in the spinal cord of mice and subsequently inhibited morphine-induced phosphorylation of NF-κB p65. In addition, a miRNA-30a-5p inhibitor decreased the levels of IL-1β and TNF-α caused by morphine in microglia.ConclusionAMPK-autophagy activation suppresses neuroinflammation and improves morphine tolerance via the upregulation of SOCS3 by inhibiting miRNA-30a-5p.

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

Results from this study5

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

01LabIn vitro (cells)Mechanism
In microglia, AICAR downregulated miRNA-30a-5p.
In plain wordsIn cells, AICAR reduced miRNA-30a-5p levels.
Peptide
AICAR (acadesine)
Outcome
DecreasemiRNA-30a-5p levels
Study
n: not reported in source
BV-2 microglia
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p.
1 context sentence(design, population, supporting numbers)
Summary · context
The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3.
Show in the study text Report a problemFND-3509311701

Studies that did not test the peptide alone4

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

02LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In microglia, AMPK activators including AICAR inhibited miRNA-30a-5p processing through autophagy.
In plain wordsIn cells, AMPK activators including AICAR inhibited miRNA-30a-5p processing.
Peptide
AICAR (acadesine)
Outcome
DecreasemiRNA-30a-5p processing
Study
n: not reported in source
BV-2 microglia
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy.
2 context sentences(design, population, supporting numbers)
Summary · context
The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p.
Summary · context
The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3509311702
03LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In microglia, AMPK activators including AICAR inhibited miRNA-30a-5p maturation through autophagy.
In plain wordsIn cells, AMPK activators including AICAR inhibited miRNA-30a-5p maturation.
Peptide
AICAR (acadesine)
Outcome
DecreasemiRNA-30a-5p maturation
Study
n: not reported in source
BV-2 microglia
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy.
2 context sentences(design, population, supporting numbers)
Summary · context
The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p.
Summary · context
The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3509311703
04LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In microglia, AMPK activators including AICAR degraded DICER through autophagy.
In plain wordsIn cells, AMPK activators including AICAR promoted DICER degradation through autophagy.
Peptide
AICAR (acadesine)
Outcome
IncreaseDICER degradation
Study
n: not reported in source
BV-2 microglia
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy.
2 context sentences(design, population, supporting numbers)
Summary · context
The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p.
Summary · context
The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3509311704
05LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In microglia, AMPK activators including AICAR degraded AGO2 through autophagy.
In plain wordsIn cells, AMPK activators including AICAR promoted AGO2 degradation through autophagy.
Peptide
AICAR (acadesine)
Outcome
IncreaseAGO2 degradation
Study
n: not reported in source
BV-2 microglia
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
We found that AMPK activators specifically inhibited the processing and maturation of miRNA-30a-5p in microglia by degrading DICER and AGO2 via autophagy.
2 context sentences(design, population, supporting numbers)
Summary · context
The AMPK activators AICAR, resveratrol and metformin downregulated miRNA-30a-5p.
Summary · context
The microglial cell line BV-2 was utilized to investigate the mechanism of AMPK-autophagy-mediated posttranscriptional regulation of SOCS3.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3509311705

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.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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