{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:00:13Z","timestamp":1787313613483,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFD1600603"],"award-info":[{"award-number":["2024YFD1600603"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of National Key Laboratory of Human Factors Engineering","award":["HFNKL2024W02"],"award-info":[{"award-number":["HFNKL2024W02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Animal models are essential for elucidating human disease mechanisms and advancing translational research. Here, we used a well-established rat tail-suspension model to investigate the pathophysiological changes associated with simulated microgravity-induced functional dyspepsia (FD) and to evaluate its utility for preclinical to clinical translation. Thirty male Wistar rats were randomly assigned to control, simulated weightlessness using hindlimb unloading (HU), and domperidone groups. The HU model was induced by 21-day tail suspension, a widely accepted ground-based platform for simulating microgravity. Behavioral tests (sucrose preference, novelty-suppressed feeding), gastrointestinal motility measurements (gastric emptying, intestinal propulsion), and serum brain\u2013gut peptide levels were assessed. Gastric and hypothalamic gene expression was analyzed by qRT-PCR. The model successfully recapitulated key FD phenotypes, including anxiety\/depression-like behaviors, reduced gastric emptying and intestinal propulsion, and systemic brain\u2013gut peptide imbalance\u2014characterized by decreased excitatory peptides [substance P (SP), gastrin (GAS), motilin (MTL), ghrelin] and increased inhibitory peptides [vasoactive intestinal peptide (VIP), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), nesfatin-1] in serum. Consistent transcriptional dysregulation was observed in gastric and hypothalamic tissues. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased, and colon 5-hydroxytryptamine (5-HT) increased, with no organic gastric lesions. Domperidone treatment significantly ameliorated behavioral abnormalities and gastrointestinal dysmotility, partially reversed brain\u2013gut peptide imbalances at both protein and transcriptional levels, and restored hippocampal BDNF. These findings demonstrate that the rat tail-suspension model provides a reproducible platform for studying microgravity-induced FD, implicating brain\u2013gut axis dysregulation. Domperidone\u2019s therapeutic effects highlight the model\u2019s utility for evaluating countermeasures against spaceflight-associated digestive dysfunction.<\/jats:p>","DOI":"10.3390\/ijms27114915","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tail-Suspension Model of Simulated Microgravity-Induced Functional Dyspepsia in Rats: Behavioral, Motility, and Brain\u2013Gut Peptide Alterations"],"prefix":"10.3390","volume":"27","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Neurobiology Laboratory, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengrui","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9490-0637","authenticated-orcid":false,"given":"Guangyou","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurobiology Laboratory, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-8415","authenticated-orcid":false,"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.2147\/DDDT.S486371","article-title":"Ginsenoside Reshapes Intestinal Microecology to Alleviate Microgravity Stress","volume":"19","author":"Wang","year":"2025","journal-title":"Drug Des. 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