Evidence map›Paper›PMID 41729391›Full record

ArticleMolecular neurobiology2026

Metformin Restores Innate Fear Deficits in Young Adult Female APP/PS1 Mice via Basolateral Amygdala Activation.

Bin Zhang, Weiming Bian, Kaiyuan Zhu, Yuzhen Dai, Miao Cai, Jiaqi Cheng, Xinyan Chen, Zheng Xiang, Yixiu Liu, Wen Lu

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Bin Zhang *Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China. zhangbin@hzcu.edu.cn.
Weiming Bian *Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Kaiyuan Zhu *Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Yuzhen Dai *Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Miao CaiKey Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hainan Medical University, Haikou, Hainan, 571199, China.
Jiaqi ChengKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Xinyan ChenKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Zheng XiangKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, China.
Yixiu LiuDepartment of Clinical Medicine, Hainan Medical University, Haikou, Hainan, 571199, China.
Wen LuKey Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hainan Medical University, Haikou, Hainan, 571199, China. swkxlw@163.com.

Funding

Key Research and Development Program of Zhejiang Province 2025C02111Natural Science Foundation of Zhejiang Province LD24H280001the National College Students' Innovative Entrepreneurial Training Plan Program of China No.202513021039The National College Students' Innovative Entrepreneurial Training Plan Program of China No.202513021031The start-up fund of Hangzhou City University To B.Z.
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by cognitive decline and neuropsychiatric symptoms, among which impaired fear responses are particularly notable. While studies have established that learned fear is compromised in AD, the status of innate fear in this context remains unclear. We found that young adult female APP/PS1 mice exhibited reduced freezing and avoidance responses to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) compared to their wild-type littermates, indicating an impaired innate fear response. Additionally, c-Fos-positive cells in the basolateral amygdala (BLA), a key region for fear processing, were significantly lower in the APP/PS1 mice. Notably, metformin treatment significantly restored TMT-induced freezing behavior and increased c-Fos-positive cells in the BLA, suggesting that it can reverse the innate fear deficit in this AD model. Mechanistically, chemogenetic inactivation of the BLA abolished the therapeutic effects of metformin on the innate fear deficit. Our study suggests metformin as a promising candidate for therapeutic intervention aimed at improving innate fear-related behavioral deficits in AD.

Indexed as

Amyloid beta-Protein PrecursorBasolateral Nuclear ComplexFearMetforminPresenilin-1Alzheimer DiseaseAnimalsAvoidance LearningBehavior, AnimalFemaleMice, Inbred C57BLMice, TransgenicProto-Oncogene Proteins c-fosAmyloid beta-Protein PrecursorMetforminPresenilin-1Proto-Oncogene Proteins c-fosAPP/PS1 miceBasolateral amygdalaChemogeneticInnate fearMetformin

Identifiers

PMID41729391

What OpenQuestion holds

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Registered trials

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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.