Evidence map›Paper›PMID 40223443›Full record

ArticleJournal of digestive diseases

DREADDs-Based Chemogenetics Induced Slow Transit Constipation via Inhibition of Enteric Neurons.

Xin Yi Lu, Yu Xiang Wen, Ni Jiang, Si Qi Zhou, Tian Yang, Liang Liang Shi, Hui Min Guo, Wei Zhang, Qi Peng Zhang, Ni Na Zhang

Abstract read
In one paragraph

Article in Journal of digestive diseases. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
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.

Xin Yi LuDepartment of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Yu Xiang WenState Key Laboratory of Pharmaceutical Biotechnology, Institute for Brain Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China.
Ni JiangNanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Si Qi ZhouDepartment of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
Tian YangDepartment of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
Liang Liang ShiDepartment of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.ORCID https://orcid.org/0000-0001-8638-9376
Hui Min GuoDepartment of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.
Wei ZhangDepartment of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China.ORCID https://orcid.org/0000-0003-0381-0773
Qi Peng ZhangState Key Laboratory of Pharmaceutical Biotechnology, Institute for Brain Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China.
Ni Na ZhangDepartment of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.ORCID https://orcid.org/0000-0002-6857-1091

Funding

Jiangsu Provincial Health Commission Medical Research General Project H2023138Nanjing Medical Key Technology Development Project ZKX22018
6 · The paper itself

Abstract

objectivesDesigner receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools are commonly used to activate or silence targeted neurons by the agonistic ligand deschloroclozapine (DCZ). This study aimed to establish a Gi-DREADD-based murine model of slow transit constipation (STC) and elucidate its pathophysiological mechanisms.

methodsAdeno-associated virus (AAV) 9-hM4Di was injected into the intestinal wall of mice, and colonic motility was evaluated. The efficiency and immunogenicity of AAV9-hM4Di transduction in the enteric nervous system (ENS) were evaluated. Nitric oxide (NO), acetylcholine (ACh), and substance P (SP) in the colonic tissues and serum samples were analyzed. Calcium (Ca

resultsAAV9-hM4Di-treated mice showed gastrointestinal motility dysfunction, including reduced fecal pellets and decreased fecal mass and water content. Electrophysiological recording of muscle contraction in the isolated colonic tissues from the chemogenetic mice showed decreased frequency and amplitude after DCZ treatment. The mice treated with AAV9-hM4Di showed the highest levels of transduction in the myenteric plexuses of the ENS. There were no differences in transduction in neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) neurons. Gi-DREADDs significantly downregulated ACh but not NO or SP expression in the distal colon in the chemogenetic mice. Ca

conclusionsIt is feasible to apply the DREADDs-based chemogenetic tools to the ENS. Gi-DREADDs can selectively modulate the ENS, inducing STC without excitatory-neural bias, offering targeted neuromodulation for gastrointestinal motility disorders.

Indexed as

ClozapineConstipationDesigner DrugsEnteric Nervous SystemNeuronsAcetylcholineAnimalsChemogeneticsColonDependovirusDisease Models, AnimalGastrointestinal MotilityGastrointestinal TransitMaleMiceMice, Inbred C57BLAcetylcholineClozapineDesigner DrugsNitric OxideSubstance Pcalcium transientdesigner receptors exclusively activated by designer drugsenteric nervous systemgastrointestinal motility

Identifiers

PMID40223443
PMCPMC12038534

What Socratic holds

Textmetadata
LicenceCC BY
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.