Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice DOI Open Access
Allen L. Pan, Mickaël Audrain,

Emmy Sakakibara

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 25, 2023

Abstract Background Dual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in causal network that regulates late-onset Alzheimer’s disease. Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating human subjects, and additionally the 5xFAD amyloidopathy mouse model. Methods AAV5-DUSP6 or AAV5-GFP (control) were stereotactically injected into dorsal hippocampus (dHc) of female male wild type mice to overexpress GFP. Spatial learning memory these assessed Barnes maze, after which hippocampal tissues isolated for downstream analysis. Results maze testing indicated overexpression dHc improved deficits associated reduced amyloid plaque load, Aß 1-40 1-42 levels, precursor processing enzyme BACE1, but not mice. Microglial activation microgliosis, mice, significantly by both males females. Transcriptomic profiling revealed upregulated expression genes involved inflammatory extracellular signal-regulated kinase (ERK) pathways, while downregulated subset pathways. A limited number differentially expressed (DEGs) (FDR<0.05) mice; ontology analysis DEGs (p<0.05) greater synaptic pathways regulated compared 5xFAD. Notably, msh homeobox 3 gene, Msx3 , previously shown regulate microglial M1/M2 polarization reduce neuroinflammation, one most robustly overexpressing DUSP6. Conclusions In summary, our data indicate deposition whereas neuroinflammation observed The sex-dependent regulation overexpression, however, improvement spatial

Language: Английский

Melittin promotes the proliferation of Schwann cells in hyperglycemic environment by up‑regulating the Crabp2/Wnt/β‑catenin signaling pathway DOI Creative Commons
Qiuyi Zhang, Yuxia Chen,

Wei Huang

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 31(1)

Published: Oct. 18, 2024

The present study aimed to explore the effect of melittin (MLT) on growth Schwann cells (SCs) in high glucose conditions and understand mechanisms involved. goal was provide a theoretical basis for using MLT treatment diabetic peripheral neuropathy (DPN). CCK‑8 assay used measure cell activity at different concentrations MLT. Flow cytometry employed analyze cycle phases apoptosis SCs under conditions. To identify differentially expressed proteins, 4D label‑free quantitative proteomics with liquid chromatography‑mass spectrometry used, followed by biological analysis potential mechanisms. PCR, western blotting immunofluorescence were conducted confirm these Melittin (0.2

Language: Английский

Citations

0
Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells DOI

Haochong Shen,

Meidi Gong,

Minghao Zhang

et al.

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 1, 2024

Abstract Background Fine particulate matter (PM2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role modulating cycle. However, precise contribution of gene BMAL1 PM2.5-induced change remains unclear. This study aims explore impact PM2.5 on expression human umbilical vein endothelial cells (HUVECs). Methods HUVECs was exposed for 24 hours at different concentrations ((0, 12.5, 25, 75 100 μg.mL-1) elucidate potential toxic mechanism. Following PM2.5, viability, ROS, cycle, key genes proteins were detected. Results A remarkable decrease viability is observed PM2.5-exposed HUVECs, as well significant increase ROS production. In addition, have arrest G0/G1 phase, p27 markedly increased. The increased significantly. Moreover, expressions p-p38 MAPK p-ERK1/2 exhibit marked HUVECs. Furthermore, following transfection siBMAL1 suppress expression, we reduction both MAPK/ERK pathway PM2.5. Conclusions Overall, our results indicate that significantly upregulates regulates through pathway, may provide new insights into molecular mechanism regarding diseases.

Language: Английский

Citations

0
Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice DOI Open Access
Allen L. Pan, Mickaël Audrain,

Emmy Sakakibara

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 25, 2023

Abstract Background Dual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in causal network that regulates late-onset Alzheimer’s disease. Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating human subjects, and additionally the 5xFAD amyloidopathy mouse model. Methods AAV5-DUSP6 or AAV5-GFP (control) were stereotactically injected into dorsal hippocampus (dHc) of female male wild type mice to overexpress GFP. Spatial learning memory these assessed Barnes maze, after which hippocampal tissues isolated for downstream analysis. Results maze testing indicated overexpression dHc improved deficits associated reduced amyloid plaque load, Aß 1-40 1-42 levels, precursor processing enzyme BACE1, but not mice. Microglial activation microgliosis, mice, significantly by both males females. Transcriptomic profiling revealed upregulated expression genes involved inflammatory extracellular signal-regulated kinase (ERK) pathways, while downregulated subset pathways. A limited number differentially expressed (DEGs) (FDR<0.05) mice; ontology analysis DEGs (p<0.05) greater synaptic pathways regulated compared 5xFAD. Notably, msh homeobox 3 gene, Msx3 , previously shown regulate microglial M1/M2 polarization reduce neuroinflammation, one most robustly overexpressing DUSP6. Conclusions In summary, our data indicate deposition whereas neuroinflammation observed The sex-dependent regulation overexpression, however, improvement spatial

Language: Английский

Citations

0