# Alpha7 nicotinic acetylcholine receptor signaling modulates ovine fetal brain astrocytes transcriptome in response to endotoxin

## TL;DR

This study shows that activating alpha7 nicotinic acetylcholine receptors in fetal sheep astrocytes can reverse pro-inflammatory gene expression caused by endotoxin, suggesting a potential neuroprotective strategy against neuroinflammation.

## Contribution

It demonstrates that alpha7nAChR agonists modulate astrocyte transcriptome towards neuroprotection in a fetal sheep model of neuroinflammation, a novel insight into fetal brain immune regulation.

## Key findings

- Alpha7nAChR agonism reverses pro-inflammatory astrocyte transcriptome.
- Alpha7nAChR antagonism enhances pro-inflammatory phenotype.
- Transcriptome analysis reveals potential neuroprotective pathways.

## Abstract

Neuroinflammation in utero may result in lifelong neurological disabilities. Astrocytes play a pivotal role, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of astrocytes. We hypothesized that agonism on alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in fetal astrocytes will augment their neuroprotective transcriptome profile, while the antagonistic stimulation of alpha7nAChR will achieve the opposite. Using an in vivo - in vitro model of developmental programming of neuroinflammation induced by lipopolysaccharide (LPS), we validated this hypothesis in primary fetal sheep astrocytes cultures re-exposed to LPS in presence of a selective alpha7nAChR agonist or antagonist. Our RNAseq findings show that a pro-inflammatory astrocyte transcriptome phenotype acquired in vitro by LPS stimulation is reversed with alpha7nAChR agonistic stimulation. Conversely, antagonistic alpha7nAChR stimulation potentiates the pro-inflammatory astrocytic transcriptome phenotype. Furthermore, we conduct a secondary transcriptome analysis against the identical alpha7nAChR experiments in fetal sheep primary microglia cultures and discuss the implications for neurodevelopment.

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Source: https://tomesphere.com/paper/1812.06617