Evidence map›Paper›PMID 42297933›Full record

ArticleMolecular psychiatry2026

NTPDase2 suppresses hippocampal astrocyte-supplied cholesterol through hydrolyzing eATP in depression.

Na Zuo, Si-Si Liu, Shu-Man Pan, Xuan-Ping Ou-Yang, Jia-Shu Yao, Yun-Long Zhou, Yi-Fan Zhou, Ling-Dong Kong, Ying Pan

Abstract read
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In one paragraph

Article in Molecular psychiatry, 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

9 authors.

Na ZuoState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Si-Si LiuState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Shu-Man PanState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Xuan-Ping Ou-YangState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Jia-Shu YaoState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Yun-Long ZhouState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Yi-Fan ZhouState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China.
Ling-Dong KongState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China. kongld@nju.edu.cn.
Ying PanState Key Laboratory of Pharmaceutical Biotechnology, Institute of Chinese Medicine, Nanjing Drum Tower Hospital, School of Life Sciences, Nanjing University, Nanjing, P.R. China. pany@nju.edu.cn.ORCID http://orcid.org/0000-0002-9477-5119

Funding

National Natural Science Foundation of China (National Science Foundation of China) No. 82174000National Natural Science Foundation of China (National Science Foundation of China) No. 82574606
6 · The paper itself

Abstract

Depression is associated with cholesterol metabolism dysregulation, but the exact correlation and underlying mechanism remain unclear. Here, our finding reveals a notable reduction in cholesterol, specifically in apolipoprotein E lipoprotein (ApoE-Lps)-carried cholesterol, in cerebrospinal fluid (CSF) of depressed rats exposing to chronic unpredictable mild stress (CUMS) or stress-level corticosterone. Consistently, Mendelian randomization (MR) analysis also showed that low level of total cholesterol in CSF may be as a risk factor associated with the characteristic symptom of depression such as anhedonia. More importantly, intracerebroventricular cholesterol administration alleviates changes in hippocampal neuronal morphology and depressive-like behaviors in CUMS rats. In astrocyte-neuron co-culture in vitro, astrocytic cholesterol release is decreased under corticosterone exposure. Mechanistically, increased nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) suppresses ATP-binding cassette G1 (ABCG1)-mediated cholesterol efflux by hydrolyzing extracellular ATP (eATP) in corticosterone-exposed astrocytes. Knockdown of Ntpdase2 in rat hippocampal astrocytes via adeno-associated virus (AAV) exhibits beneficial effects in increasing hippocampal neuronal cholesterol level, protecting neuronal morphology and improving depressive-like behaviors compared with vehicle-injected corticosterone model. Collectively, this study suggests impaired astrocytic cholesterol efflux as a cause of abnormality in hippocampal neuronal structure and identifies NTPDase2 as a potential therapeutic target for depression.

Indexed as

Adenosine TriphosphatasesCholesterolDepressionAdenosine TriphosphateAnimalsApolipoproteins EAstrocytesCorticosteroneDisease Models, AnimalHippocampusMaleNeuronsRatsRats, Sprague-DawleyStress, PsychologicalAdenosine TriphosphatasesAdenosine TriphosphateApolipoproteins ECholesterolCorticosteroneectoATPase

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

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.