Long-term voluntary running improves cognitive ability in developing mice by modulating the cholinergic system, antioxidant ability, and BDNF/PI3K/Akt/CREB pathway.

Moderate physical exercise has positive effects on memory. The present study aimed to investigate the impact of long-term exercise on spatial memory in developing mice, as well as its association with the cholinergic system, antioxidant activities, apoptosis factor, and BDNF/PI3K/Akt/CREB pathway in the brain. In this study, Y maze and Novel object recognition (NOR) tests were employed to assess the impact of long-term voluntary exercise on memory. The cholinergic system, antioxidant activities, and apoptosis factors in the brain were quantified using Elisa. Additionally, western blot analysis was conducted to determine the expression of relevant proteins in the BDNF/PI3K/Akt/CREB pathway. The findings demonstrated that prolonged voluntary wheel running exercise enhanced memory in developing mice, concomitant with increased catalase (CAT) activity and decreased malondialdehyde (MDA) levels in the brain. Moreover, it could also increase the hippocampal acetylcholine (ACh) content and suppress the expression of neuronal apoptosis protein. Additionally, exercise also upregulated the expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphoinositide 3 kinases (PI3K), Akt, cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These findings suggest that long-term voluntary wheel running exercise improves the spatial memory of developing mice by modulating the cholinergic system, antioxidant activities, apoptosis factors, and activating the BDNF/PI3K/Akt/CREB pathway.

Voluntary exercise during puberty promotes spatial memory and hippocampal DG/CA3 synaptic transmission in mice.

Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.

Effect of voluntary wheel running on gut microbiota composition in developing mice.

Introduction: Background: exercise can increase the species and quantity of beneficial gut microbiota, enrich the diversity of microflora, and promote the development of symbiotic bacteria, especially in the stage of ontogeny. However, there is little evidence of the short-term voluntary exercise effect on the gut microbiota in developing mice. Material and method: therefore, we used short-term voluntary wheel running model to study the gut microbiota of developing mice (1 month old), and detected the fecal samples by 16S rRNA gene sequencing. Results: the results showed that after 4 weeks of voluntary wheel running, the body weight of the running group was significantly lower than that of the control group. Conclusion: there was a significant separation between the running group and the control group in beta diversity measures. At the family level, the clostridiales flora of the running group was higher than that of the control group. Compared with the control group, the abundance of parabacteroides flora and anaerovorax flora increased significantly, and the abundance of anaerotruncus flora and odoribacter flora decreased significantly in the running group. These results showed that gut microbiota be affected after short-term voluntary wheel running in developing mice.

Introducción: Introducción: el ejercicio puede aumentar las especies y la cantidad de microbiota intestinal beneficiosa, enriquecer la diversidad de la microflora y promover el desarrollo de bacterias simbióticas, especialmente en la etapa de ontogenia. Sin embargo, hay poca evidencia del efecto del ejercicio voluntario a corto plazo sobre la microbiota intestinal en ratones en desarrollo. Material y método: por lo tanto, utilizamos un modelo de carrera de ruedas voluntario a corto plazo para estudiar la microbiota intestinal de ratones en desarrollo (1 mes de edad) y detectamos las muestras fecales mediante la secuenciación del gen 16S rRNA. Resultados: los resultados mostraron que después de 4 semanas de carrera voluntaria con ruedas, el peso corporal del grupo de carrera fue significativamente más bajo que el del grupo de control. Conclusión: hubo una diferencia significativa entre el grupo de corredores y el grupo de control en las medidas de diversidad beta. A nivel familiar, la flora de clostridiales del grupo de corredores fue mayor que la del grupo de control. En comparación con el grupo de control, la abundancia de flora parabacteroides y flora anaerovorax aumentó significativamente, y la abundancia de flora anaerotruncus y flora odoribacter disminuyó significativamente en el grupo de carrera. Estos resultados mostraron que la microbiota intestinal se ve afectada después de la carrera voluntaria a corto plazo en ratones en desarrollo.

Pectolinarigenin reduces the expression of sterol regulatory element-binding proteins and cellular lipid levels.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that have important roles in the genes involved in lipid biosynthesis. In this study, it was found that the flavonoid pectolinarigenin, reduced the activity of SRE-containing fatty acid synthase (FAS) promoter and the mRNA expressions of SREBP target genes in human hepatoma (Huh-7) cells. Moreover, compared with other flavonoids, pectolinarigenin reduced the mature forms of SREBPs in a dose-dependent manner. The insulin-induced gene (INSIG) and proteasome were not involved in the pectolinarigenin-mediated reduction of mature forms of SREBPs. Pectolinarigenin also reduced the lipid contents in vitro. These results suggest that pectolinarigenin may inhibit lipogenesis through suppressing SREBP activity, at least partially, via the formation of SREBPs mature forms, thereby reducing the expression of their downstream genes related to lipogenesis. To the best of our knowledge, this is the first work that shows how pectolinarigenin affects cellular lipid levels by affecting SREBPs.