Evidence map›Paper›PMID 40293704›Full record

ArticleMolecular neurobiology2025

Melatonin Mitigates Sleep Restriction-Induced Cognitive and Glymphatic Dysfunction Via Aquaporin-4 Polarization.

Huaiqing Sun, Qiuchen Cao, Xiaoxin He, Xinyu Du, Xueqin Jiang, Ting Wu, Ming Xiao

Abstract read
PubMed Publisher
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 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–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

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

7 authors.

Huaiqing SunDepartment of Neurology, the First Affiliated Hospital With Nanjing Medical University Nanjing, Jiangsu, 210029, China.
Qiuchen CaoJiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Jiangsu, Nanjing, 211166, China.
Xiaoxin HeJiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Jiangsu, Nanjing, 211166, China.
Xinyu DuDepartment of Neurology, the First Affiliated Hospital With Nanjing Medical University Nanjing, Jiangsu, 210029, China.
Xueqin JiangDepartment of Neurology, the First Affiliated Hospital With Nanjing Medical University Nanjing, Jiangsu, 210029, China.
Ting WuDepartment of Neurology, the First Affiliated Hospital With Nanjing Medical University Nanjing, Jiangsu, 210029, China. wuting80000@njmu.edu.cn.
Ming XiaoJiangsu Province Key Laboratory of Neurodegeneration, Nanjing Medical University, Jiangsu, Nanjing, 211166, China. mingx@njmu.edu.cn.

Funding

the Jiangsu Municipal Science and Technology Bureau BE2017734the Key Project of Jiangsu Province's Key Research and Development Program BE2023023-2the National Natural Science Foundation of China 81772454the Postgraduate Research and Practice Innovation Program of Jiangsu Province SJCX24_0773
6 · The paper itself

Abstract

Chronic sleep restriction (SR) impairs the glymphatic clearance of macromolecular toxic metabolites, which is associated with the loss of perivascular polarization of aquaporin-4 (AQP4). Melatonin (Mel) has been shown to maintain the circadian rhythm of AQP4 polarization. However, the role of AQP4 polarization in Mel's protective effects against SR-induced brain dysfunction remains unclear. In the present study, using a modified rotating rod SR mouse model, we demonstrated the time-dependent effect of SR on short-term memory deficits and AQP4 mislocalization in the hippocampus. Subsequent experiments characterized the dose-dependent pattern of Mel ameliorating SR-induced impairments of cognitive function and AQP4 polarity. Mel's treatment enhanced glymphatic transport in SR mice, as revealed by cerebrospinal tracer experiments, and reduced hippocampal amyloid-beta and phosphorylated tau levels. Additionally, Mel significantly decreased glial cell activation, pro-inflammatory cytokine production, and synaptic protein loss in the hippocampus of SR mice. However, in AQP4 knockout mice, Mel's protective effects against SR-induced pathophysiological alterations described above were largely abolished. Mechanistically, Mel activated the vitamin D receptor and then upregulated expression of DTNA (Dystrobrevin Alpha), a key component of the dystrophin-associated complex, which in turn restored AQP4 polarization during chronic SR conditions. This finding indicates that AQP4-mediated lymphatic clearance is necessary for Mel to combat chronic SR-induced brain impairment.

Indexed as

Aquaporin 4CognitionGlymphatic SystemMelatoninSleep DeprivationAnimalsHippocampusMaleMiceMice, Inbred C57BLMice, KnockoutAqp4 protein, mouseAquaporin 4MelatoninAquaporin 4Cognitive impairmentGlymphatic systemMelatoninSleep restriction

Identifiers

PMID40293704

What OpenQuestion holds

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Read underepoch 390

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.