Evidence map›Paper›PMID 41944308›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

An Activity-Dependent NEPAS-PTX3 Axis Links Neurovascular and Myelin Deficits to Cognitive Impairment.

Boya Hu, Zifei Chen, Bingmei Sun, Jiale Gao, Jiale Xu, Xiaochun Guo, Fenfei Gao, Zhongsi Wang, Jie Wu, Xiaoyu Ji and 2 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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

12 authors.

Boya HuDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Zifei ChenDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Bingmei SunDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Jiale GaoDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Jiale XuDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Xiaochun GuoDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Fenfei GaoDepartment of Pharmacology, Shantou University Medical College, Shantou, Guangdong, China.
Zhongsi WangBeijing SeqWisdom Biotechnology Co., Ltd., Beijing, China.
Jie WuDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Xiaoyu JiDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Peipei LiuClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Bing HuangDepartment of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.ORCID https://orcid.org/0000-0001-5138-1446

Funding

Guangdong Basic and Applied Basic Research Foundation 2023B1515230008Henan Province Project for Cultivating Talents in Health Science and Technology Innovation for Middle-aged and Young People JQRC2025008National Natural Science Foundation of China 82571622Natural Science Foundation of Guangdong Province 2024A1515011463Natural Science Foundation of Guangdong Province B2024065Natural Science Foundation of Henan Province 252300420095Young Scientists Fund of the National Natural Science Foundation of China 82201629
6 · The paper itself

Abstract

Acquired cognitive impairments occur in diverse neurological and psychiatric conditions, yet the mechanisms linking neural circuit activity to neurovascular function remain poorly understood. Using a mouse model of nicotine withdrawal (WD), we identified an activity-dependent NEPAS-pentraxin-3 (PTX3) axis in mPFC neurons that couples circuit hypoactivity to cognitive deficits. In this model, NEPAS expression is significantly upregulated in mPFC neurons, accompanied by reduced myelin formation. Neuronal activity in mPFC and PVA is suppressed and chemogenetic activation of the PVA-mPFC neural circuit downregulates NEPAS. Elevated neuronal NEPAS suppresses the secretion of PTX3, thereby impairing angiogenesis. Conversely, knockdown of neuronal NEPAS restores PTX3 expression and angiogenesis, alleviates myelin formation deficits, and improves cognitive memory following nicotine WD. Notably, activation of the PVA-mPFC neural circuit produces similar therapeutic effects. Human transcriptomic data reveal a consistently elevated HIF-3α expression in ex-smokers versus controls. Our findings demonstrate that the NEPAS-PTX3 axis in mPFC neurons links neural circuit hypoactivity to neurovascular and myelin deficits, providing a mechanistic framework for acquired cognitive impairment. This pathway represents a potential target for neuromodulation-based therapies in prefrontal circuit dysfunction associated cognitive disorders.

Indexed as

Cognitive DysfunctionC-Reactive ProteinMyelin SheathNerve Tissue ProteinsSerum Amyloid P-ComponentAnimalsDisease Models, AnimalHumansMaleMiceNeuronsNicotinePentraxinsPrefrontal CortexC-Reactive ProteinNerve Tissue ProteinsNicotinePentraxinsSerum Amyloid P-Componentcognitive deficitsmedial prefrontal cortex (mPFC)myelinationNEPASneurovascular couplingpentraxin‐3 (PTX3)

Identifiers

PMID41944308
PMCPMC13334678

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.