Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Objective: Precise knowledge regarding the mechanical stress applied to the intervertebral disc following each individual spine motion enables physicians and patients to understand how people with discogenic back pain should be guided in their exercises and which spine motions to specifically avoid. We created an intervertebral disc degeneration model and conducted a finite element (FE) analysis of loaded stresses following each spinal posture or motion. Methods: A 3-dimensional FE model of intervertebral disc degeneration at L4–5 was constructed. The intervertebral disc degeneration model was created according to the modified Dallas discogram scale. The von Mises stress and range of motion (ROM) regarding the intervertebral discs and the endplates were analyzed. Results: We observed that mechanical stresses loaded onto the intervertebral discs were similar during flexion, extension, and lateral bending, which were greater than those occurring during torsion. Based on the comparison among the grades divided by the modified Dallas discogram scale, the mechanical stress during extension was greater in grades 3–5 than it was during the others. During extension, the mechanical stress loaded onto the intervertebral disc and endplate was greatest in the posterior portion. Mechanical stresses loaded onto the intervertebral disc were greater in grades 3–5 compared to those in grades 0–2. Conclusion Our findings suggest that it might be beneficial for patients experiencing discogenic back pain to maintain a neutral posture in their lumbar spine when engaging in daily activities and exercises, especially those suffering from significant intravertebral disc degeneration.

Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of “responses to stress or steroid hormones”, “histone modification”, and “regulating MAPK signaling pathways”. While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.