# Temporal Shifts in MicroRNAs Signify the Inflammatory State of Primary Murine Microglial Cells

## TL;DR

This study shows how microRNA levels change over time in microglial cells during inflammation and how a drug called ladostigil can influence these changes.

## Contribution

The study identifies specific microRNAs with temporal regulation in microglial inflammation and demonstrates the modulatory effect of ladostigil.

## Key findings

- bzATP and LPS triggered increased interleukin and chemokine expression in microglial cells.
- Ladostigil upregulated anti-inflammatory miRNAs like miR-27a, miR-27b, and miR-23b at 8 h post-activation.
- Temporal regulation of miRNAs such as miR-155 and miR-146b was observed in inflammatory pathways.

## Abstract

The primary function of microglia is to maintain brain homeostasis. In neurodegenerative diseases like Alzheimer’s, microglia contribute to neurotoxicity and inflammation. In this study, we exposed neonatal murine primary microglial cultures to stimuli mimicking pathogens, injury, or toxins. Treatment with benzoyl ATP (bzATP) and lipopolysaccharide (LPS) triggered a coordinated increase in interleukin and chemokine expression. We analyzed statistically significant differentially expressed microRNAs (DEMs) at 3 and 8 h post-activation, identifying 33 and 57 DEMs, respectively. Notably, miR-155, miR-132, miR-3473e, miR-222, and miR-146b showed strong temporal regulation, while miR-3963 was sharply downregulated by bzATP. These DEMs regulate inflammatory pathways, including TNFα and NFκB signaling. We also examined the effect of ladostigil, a neuroprotective agent known to reduce oxidative stress and inflammation. At 8 h post-activation, ladostigil induced upregulation of anti-inflammatory miRNAs, such as miR-27a, miR-27b, and miR-23b. Our findings suggest that miRNA profiles reflect microglial responses to inflammatory cues and that ladostigil modulates these responses. This model of controlled microglial activation offers a powerful tool with which to study inflammation in the aging brain and the progression of neurodegenerative diseases.