Evidence map›Paper›PMID 41307793›Full record

ArticleMolecular neurobiology2025

AMPK Activation by ENERGI Ameliorates Behavioral and Synaptic Deficits in a Mouse Model of Autism.

Ming-Chia Chu, Chi-Chun Wu, Yueh-Jung Chung, Chieh-Yu Chang, Han-Fang Wu, Sze-Chi Tsai, Tzu-Ning Peng, Tzu-Jung Yang, Hui-Ching Lin

Abstract read
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ming-Chia ChuDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Chi-Chun WuDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Yueh-Jung ChungDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Chieh-Yu ChangDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Han-Fang WuDepartment of Optometry, MacKay Medical College, New Taipei City, Taiwan.
Sze-Chi TsaiDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Tzu-Ning PengDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Tzu-Jung YangDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Hui-Ching LinDepartment and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. hclin7@nycu.edu.tw.ORCID http://orcid.org/0000-0002-1639-9293

Funding

Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education, Taiwan 114W032101; 113W032101Energenesis Biomedical CO., LTD., Taiwan 112A40078T; 109J061Ministry of Education (MOE) in Taiwan under the Higher Education Sprout Project DP2-TMU-114-N-01National Science and Technology Council NSTC 114-2320-B-A49-001; NSTC 113-2320-B-A49-003; NSTC 112-2320-B-A49-008-MY3; NSTC 112-2320-B-A49-048; NSTC 111-2811-B-A49A-043; NSTC 111-2320-B-A49-008; NSTC 111-2320-B-A49-037; MOST 111-2811-B-A49A-004; MOST 110-2320-B-A49A-503; MOST 110-2628-B-A49A-504"National Yang Ming Chiao Tung University-Far Eastern Memorial Hospital Joint Research Program'', Taiwan #NYCU-FEMH 114DN08; #NYCU-FEMH 113DN08
6 · The paper itself

Abstract

Autism spectrum disorder (ASD), a neurodevelopmental disorder, is characterized by synaptic dysregulation as its underlying pathophysiological mechanism. AMP-activated protein kinase (AMPK), an intracellular energy sensor, plays a pivotal role in regulating synaptic integrity and function. Current treatments for ASD exhibit limited benefits in alleviating the core symptoms of ASD. Consequently, we investigated the therapeutic potential of ENERGI, a novel AMPK-activating compound, in a valproate (VPA)-induced mouse model of ASD. ENERGI was administered via drinking water to VPA-induced ASD offspring. After 7 days of treatment, ENERGI gradually alleviated social defects, repetitive behaviors, and emotional comorbidities in VPA-induced ASD offspring. At the synaptic level, ENERGI treatment restored aberrant plasticity, spine structure, and dendritic arborization in the hippocampus of VPA-induced ASD offspring. Notably, the curative effects of ENERGI in VPA-induced ASD offspring were equivalent to those of D-cycloserine (DCS), a known therapeutic candidate for ASD. Moreover, ENERGI demonstrated superior efficacy in restoring spine abnormalities than DCS. Mechanistically, 7-day ENERGI treatment reversed the reduction in AMPK phosphorylation, and normalized the elevated PSD95 and synaptic GluA2 levels in VPA-induced ASD offspring, whereas DCS treatment only rescued the synaptic GluA2 levels. Overall, these findings suggest that AMPK activation by ENERGI effectively reverses behavioral and synaptic deficits in a preclinical ASD model, supporting AMPK as a promising target for developing novel ASD therapies.

Indexed as

AMP-Activated Protein KinasesAutistic DisorderBehavior, AnimalSynapsesAnimalsAutism Spectrum DisorderDendritic SpinesDisease Models, AnimalEnzyme ActivationFemaleHippocampusMaleMiceMice, Inbred C57BLNeuronal PlasticityValproic AcidAMP-Activated Protein KinasesValproic AcidAMP-activated protein kinase (AMPK)Autism spectrum disorderDendritic spine morphologySynaptic plasticityValproate-induced autism model

Identifiers

PMID41307793
PMCPMC12660476

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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.