Temporal shifts in microRNAs signify the inflammatory state of primary murine microglial cells DOI Creative Commons
Keren Zohar, Elyad Lezmi,

Fanny Reichert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract The primary function of microglia is to maintain brain homeostasis. However, in several neurodegenerative diseases, such as Alzheimer’s disease, the pathophysiological hallmarks that drive disease progression involve neurotoxicity and alterations neuroinflammation. In this study, we exposed murine neonatal microglial cultures external signals mimic vivo stimuli caused by pathogens, injury, or toxic agents. presence benzoyl ATP (bzATP) lipopolysaccharide (LPS), observed a coordinated increase expression interleukins chemokines. We focused on dynamics differentially expressed microRNAs (miRNAs) are statistically significant (DEMs) tracked their post-activation dynamics. Monitoring miRNAs 3 8 hours (h) revealed robust changes 33 57 DEMs, most which were upregulated. DEMs exhibiting strongest temporal regulation included miR-155, miR-132, miR-3473e, miR-222, miR-146b. Additionally, strong downregulation miR-3963 was attributed exposure bzATP. Through TNFα NFκB signaling pathways, identified reflect cellular response inflammatory signals. incubated activated cells with ladostigil, neuroprotective compound has been shown reduce oxidative stress, inflammation, cognitive decline. While there no effect h post-activation, at h, few implicated inflammation suppression miR-27a, miR-27b, miR-23b upregulated ladostigil-dependent manner. conclude miRNA profile provides sensitive indicator regulatory mechanisms underlying inflammation-related responses microglia. propose subjected controlled activation paradigms can serve model for states monitor aging along diseases.

Language: Английский

Exosomes in Regulating miRNAs for Biomarkers of Neurodegenerative Disorders DOI
Azhagu Madhavan Sivalingam,

Darshitha D Sureshkumar

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

Citations

1
Characterization of Isolated Human Astrocytes from Aging Brain DOI Open Access
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3416 - 3416

Published: April 5, 2025

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain's internal milieu eventually impact neuronal function lead neurodegeneration. Until now, most evidence of astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived animal models lines. In this study, we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's (ADD), progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Language: Английский

Citations

0
Temporal shifts in microRNAs signify the inflammatory state of primary murine microglial cells DOI Creative Commons
Keren Zohar, Elyad Lezmi,

Fanny Reichert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract The primary function of microglia is to maintain brain homeostasis. However, in several neurodegenerative diseases, such as Alzheimer’s disease, the pathophysiological hallmarks that drive disease progression involve neurotoxicity and alterations neuroinflammation. In this study, we exposed murine neonatal microglial cultures external signals mimic vivo stimuli caused by pathogens, injury, or toxic agents. presence benzoyl ATP (bzATP) lipopolysaccharide (LPS), observed a coordinated increase expression interleukins chemokines. We focused on dynamics differentially expressed microRNAs (miRNAs) are statistically significant (DEMs) tracked their post-activation dynamics. Monitoring miRNAs 3 8 hours (h) revealed robust changes 33 57 DEMs, most which were upregulated. DEMs exhibiting strongest temporal regulation included miR-155, miR-132, miR-3473e, miR-222, miR-146b. Additionally, strong downregulation miR-3963 was attributed exposure bzATP. Through TNFα NFκB signaling pathways, identified reflect cellular response inflammatory signals. incubated activated cells with ladostigil, neuroprotective compound has been shown reduce oxidative stress, inflammation, cognitive decline. While there no effect h post-activation, at h, few implicated inflammation suppression miR-27a, miR-27b, miR-23b upregulated ladostigil-dependent manner. conclude miRNA profile provides sensitive indicator regulatory mechanisms underlying inflammation-related responses microglia. propose subjected controlled activation paradigms can serve model for states monitor aging along diseases.

Language: Английский

Citations

0