Zheng Yumei, Yu Yanan, Chen Mengyao, Zhang Huiyuan, Wang Wanzhao, Fan Xiushan, Sun Lijun, Tang Liang, Ta Dean
Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China.
Center for Biomedical Engineering, School of Information Science and Technology, Fudan University, Shanghai, 200433, China.
Mol Neurobiol. 2025 Jun;62(6):7313-7329. doi: 10.1007/s12035-025-04709-8. Epub 2025 Jan 29.
Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.
失重通常会导致肠道微生物群紊乱，并损害认知功能。肠道微生物群与神经系统疾病之间存在密切联系。低强度脉冲超声（LIPUS）对减轻肠道炎症有有益作用。因此，我们想知道腹部LIPUS刺激是否可以通过减少肠道功能障碍对失重诱导的认知衰退产生积极影响。研究结果显示，后肢卸载小鼠的肠道结构和肠道微生物稳态出现明显紊乱，同时其学习和记忆能力受损。然而，为期4周的腹部LIPUS治疗改善了后肢卸载小鼠的肠道功能，其特征为结肠中紧密连接蛋白ZO-1和闭合蛋白表达上调、肠道微生物群的多样性和丰度增加、血清脂多糖（LPS）降低以及结肠内容物中短链脂肪酸增加。接受LIPUS治疗的后肢卸载小鼠表现出活动水平提高、探索倾向改善、学习和记忆能力显著增强，以及海马体中PSD95、GAP43、P-CREB、BDNF及其受体TRKB等神经适应性相关蛋白的表达升高。此外，接受来自腹部接受LIPUS照射小鼠粪便移植的后肢卸载小鼠表现出认知能力增强和肠道结构改善，类似于直接接受腹部LIPUS治疗的后肢卸载小鼠所观察到的结果。上述结果表明，LIPUS可增强肠道结构和微生物群，有助于减轻失重引起的认知障碍。LIPUS可能是一种同时改善宇航员或卧床患者肠道功能障碍和认知衰退的潜在策略。
