1.Intermittent MDMA Attenuates Ovariectomy-induced Bone Loss via a Gut Microbiota–Bone Axis
Xiayun WAN ; Akifumi EGUCHI ; Rumi MURAYAMA ; Chisato MORI ; Kenji HASHIMOTO
Clinical Psychopharmacology and Neuroscience 2025;23(4):668-682
Objective:
3,4-Methylenedioxymethamphetamine (MDMA) is widely used recreationally but also modulates serotonergic signaling in the gut, potentially influencing the microbiota. Because low bone mineral density (BMD) is common in depression and other psychiatric disorders, we tested whether repeated, intermittent MDMA attenuates BMD loss in ovariectomized (OVX) mice.
Methods:
OVX mice received MDMA (10 mg/kg) three times per week for six weeks. BMD was measured, and untargeted metabolomics of plasma samples along with gut microbiota profiling of fecal samples were performed.
Results:
Compared with vehicle, MDMA increased whole-body and femoral BMD and shifted circulating bone-remodeling markers toward an antiresorptive profile—lower receptor activator of nuclear factor-κB ligand (RANKL) and higher osteoprotegerin. Gut microbiota profiling and untargeted metabolomics showed reduced Clostridia and enrichment of Bacilli, along with a marked decrease in plasma β-D-allose, a metabolite linked to Lactobacillus johnsonii.
Conclusion
These findings suggest that intermittent MDMA may mitigate OVX-induced BMD loss in association with remodeling of a gut microbiota–bone axis. Future studies should define causal microbial and metabolic mediators and evaluate generalizability across additional bone-loss models.
2.Autism-like Behaviors in Male Juvenile Offspring after Maternal Glyphosate Exposure
Yaoyu PU ; Li MA ; Jiajing SHAN ; Xiayun WAN ; Bruce D. HAMMOCK ; Kenji HASHIMOTO
Clinical Psychopharmacology and Neuroscience 2021;19(3):554-558
Objective:
Exposure to the herbicide glyphosate during pregnancy and lactation may increase the risk for autism spectrum disorder (ASD) in offspring. Recently, we reported that maternal exposure of formulated glyphosate caused ASD-like behaviors in juvenile offspring. Here, we investigated whether maternal exposure of pure glyphosate could cause ASD-like behaviors in juvenile offspring.
Methods:
Water or 0.098% glyphosate was administered as drinking water from E5 to P21 (weaning). Behavioral tests such as grooming test and three-chamber social interaction test in male offspring were performed from P28 to P35.
Results:
Male offspring showed ASD-like behavioral abnormalities (i.e., increasing grooming behavior and social interaction deficit) after maternal exposure of glyphosate.
Conclusion
The findings suggest that the exposure of glyphosate during pregnancy and lactation may cause ASD-like behavioral abnormalities in male juvenile offspring. It is likely that glyphosate itself, but not the other ingredients, may contribute to ASD-like behavioral abnormalities in juvenile offspring.
3.Autism-like Behaviors in Male Juvenile Offspring after Maternal Glyphosate Exposure
Yaoyu PU ; Li MA ; Jiajing SHAN ; Xiayun WAN ; Bruce D. HAMMOCK ; Kenji HASHIMOTO
Clinical Psychopharmacology and Neuroscience 2021;19(3):554-558
Objective:
Exposure to the herbicide glyphosate during pregnancy and lactation may increase the risk for autism spectrum disorder (ASD) in offspring. Recently, we reported that maternal exposure of formulated glyphosate caused ASD-like behaviors in juvenile offspring. Here, we investigated whether maternal exposure of pure glyphosate could cause ASD-like behaviors in juvenile offspring.
Methods:
Water or 0.098% glyphosate was administered as drinking water from E5 to P21 (weaning). Behavioral tests such as grooming test and three-chamber social interaction test in male offspring were performed from P28 to P35.
Results:
Male offspring showed ASD-like behavioral abnormalities (i.e., increasing grooming behavior and social interaction deficit) after maternal exposure of glyphosate.
Conclusion
The findings suggest that the exposure of glyphosate during pregnancy and lactation may cause ASD-like behavioral abnormalities in male juvenile offspring. It is likely that glyphosate itself, but not the other ingredients, may contribute to ASD-like behavioral abnormalities in juvenile offspring.

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