{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:42:58Z","timestamp":1791517378964,"version":"4.3.4"},"reference-count":121,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Opening Funding of the National Key Laboratory of Electromagnetic Space Security","award":["JCKY2024240C006"],"award-info":[{"award-number":["JCKY2024240C006"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Microgravity exposure during spaceflight has been linked to cognitive impairments, including deficits in attention, executive function, and spatial memory. Both space missions and ground-based analogs\u2014such as head-down bed rest, dry immersion, and hindlimb unloading\u2014consistently demonstrate that altered gravity disrupts brain structure and neural plasticity. Neuroimaging data reveal significant changes in brain morphology, functional connectivity, and cerebrospinal fluid dynamics. At the cellular level, simulated microgravity impairs synaptic plasticity, alters dendritic spine architecture, and compromises neurotransmitter release. These changes are accompanied by dysregulation of neuroendocrine signaling, decreased expression of neurotrophic factors, and activation of oxidative stress and neuroinflammatory pathways. Molecular and omics-level analyses further point to mitochondrial dysfunction and disruptions in key signaling cascades governing synaptic integrity, energy metabolism, and neuronal survival. Despite these advances, discrepancies across studies\u2014due to differences in models, durations, and endpoints\u2014limit mechanistic clarity and translational relevance. Human data remain scarce, emphasizing the need for standardized, longitudinal, and multimodal investigations. This review provides an integrated synthesis of current evidence on the cognitive and neurobiological effects of microgravity, spanning behavioral, structural, cellular, and molecular domains. By identifying consistent patterns and unresolved questions, we highlight critical targets for future research and the development of effective neuroprotective strategies for long-duration space missions.<\/jats:p>","DOI":"10.3390\/ijms26199521","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Spaceflight and Ground-Based Microgravity Simulation Impact on Cognition and Brain Plasticity"],"prefix":"10.3390","volume":"26","author":[{"given":"Jiaqi","family":"Hao","sequence":"first","affiliation":[{"name":"School of Medical Technology, Beijing Institute of Technology, Beijing 100811, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-1956","authenticated-orcid":false,"given":"Jun","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Beijing Institute of Technology, Beijing 100811, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-4052","authenticated-orcid":false,"given":"Yulin","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Beijing Institute of Technology, Beijing 100811, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dinatolo, M.F., and Cohen, L.Y. 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