Evidence map›Paper›PMID 40462081›Full record

ArticleBMC medicine2025

Lactate links exercise to synaptic protection and cognitive enhancement in Alzheimer's disease models.

Hao Han, Yi Wu, Ru Mi, Cijia Zhang, Fengying Guan, Xiaoyan Lu, Guangwei Zhang, Zhaojie Meng, Li Chen, Ming Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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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

10 authors.

Hao HanDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China.
Yi WuJilin Provincial Institute of Pharmaceutical Research, Changchun, 130061, China.
Ru MiDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China.
Cijia ZhangDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China.
Fengying GuanDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China.
Xiaoyan LuThe Second Hospital of Jilin University, Changchun, 130041, China.
Guangwei ZhangThe First Hospital of Jilin University, Changchun, 130031, China.
Zhaojie MengState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, China.
Li ChenDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China.
Ming ZhangDepartment of Pharmacology, College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 126 Xin Min Street, Changchun, Jilin, 130021, China. zhangming99@jlu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPhysical exercise is known to promote cognitive resilience in aging and Alzheimer's disease (AD), but the underlying mechanisms remain incompletely understood. Lactate, a metabolic byproduct elevated during exercise, has recently emerged as a potential neuromodulator of brain function.

methodsThree AD-like mouse models (SAMP8, Aβ1-42 injection, and 5xFAD) were used to evaluate the effects of treadmill exercise on cognitive function and synaptic plasticity. Serum lactate levels were assessed, and sodium L-lactate (NaLA) was administered to determine its neuroprotective effects. Transcriptomic analysis was performed on hippocampal tissue to explore lactate-regulated pathways. Lactate transport was pharmacologically inhibited using 4-CIN for mechanistic validation.

resultsTreadmill exercise significantly improved cognitive performance and increased synapse-associated protein expression in AD models. Exercise elevated serum lactate levels, and exogenous NaLA administration recapitulated the cognitive and synaptic benefits of exercise. Transcriptomic profiling revealed enrichment of genes involved in axon guidance and synaptic organization, including upregulation of multiple Eph receptor family genes. α-cyano-4-hydroxycinnamic acid (4-CIN) administration abolished the exercise-induced neuroprotective effects, confirming the essential role of lactate transport in mediating these benefits.

conclusionsThis study identifies lactate as a critical mediator linking exercise to enhanced synaptic function and cognitive improvement in AD-like models, providing mechanistic insights and highlighting lactate metabolism as a potential therapeutic target for AD.

Indexed as

Alzheimer DiseaseCognitionLactic AcidPhysical Conditioning, AnimalSynapsesAnimalsDisease Models, AnimalHippocampusMaleMiceNeuronal PlasticityLactic AcidAlzheimer’s diseaseAxon guidanceCognitive functionExerciseLactateSynaptic plasticity

Identifiers

PMID40462081
PMCPMC12135605

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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.