Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota

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.