BACKGROUND: The mammalian target of rapamycin (mTOR) signaling is critical for the maintenance and differentiation of neurogenesis, and conceivably for many other brain developmental processes. However, in vivo studies of mTOR functions in the brain are often hampered due to the essential role of the associated signaling in brain development. METHODS: We monitored the long- and short-term effects of mTOR signaling regulation on cerebral organoids growth, differentiation and function using an mTOR inhibitor (everolimus) and an mTOR activator (MHY1485). RESULTS: Short-term treatment with MHY1485 induced faster organoid growth and differentiation, while long-term treatment induced the maturation of cerebral organoids. CONCLUSION These data suggest that the optimal activity of mTOR is crucial in maintaining normal brain development, and its role is not confined to the early neurogenic phase of brain development.

BACKGROUND: Microplastics (MPs) are small fragments from any type of plastic formed from various sources, including plastic waste and microfibers from clothing. MPs degrades slowly, resulting in a high probability of human inhalation, ingestion and accumulation in bodies and tissues. As its impact on humans is a prolonged event, the evaluation of its toxicity and influence on human health are critical. In particular, MPs can enter the human digestive system through food and beverage consumption, and its effect on the human colon needs to be carefully examined. METHODS: We monitored the influence of small MPs (50 and 100 nm) on human colon cells, human colon organoids and also examined their toxicity and changes in gene expression in vivo in a mouse model. RESULTS: The data suggested that 5 mg/mL concentrations of 50 and 100 nm MPs induced a[ 20% decrease in colon organoid viability and an increase in the expression of inflammatory-, apoptosis- and immunity-related genes. In addition, in vivo data suggested that 50 nm MPs accumulate in various mouse organs, including the colon, liver, pancreas and testicles after 7 d of exposure. CONCLUSION Taken together, our data suggest that smaller MPs can induce more toxic effects in the human colon and that human colon organoids have the potential to be used as a predictive tool for colon toxicity.

Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.

Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.

Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.