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 \alpha 7 nicotinic acetylcholine receptor ( \alpha 7nAChR ) in fetal astrocytes will augment their neuroprotective transcriptome profile, while the antagonistic stimulation of \alpha 7nAChR 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 \alpha 7nAChR agonist or antagonist. Our RNAseq findings show that a pro-inflammatory astrocyte transcriptome phenotype acquired in vitro by LPS stimulation is reversed with \alpha 7nAChR agonistic stimulation. Conversely, antagonistic \alpha 7nAChR stimulation potentiates the pro-inflammatory astrocytic transcriptome phenotype. Furthermore, we conduct a secondary transcriptome analysis against the identical \alpha 7nAChR experiments in fetal sheep primary microglia cultures and against the Simons Simplex Collection for autism spectrum disorder and discuss the implications  .
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 .
D
\alpha
R
7
alpha7
D
\alpha
R
7nAChR
alpha7nAChR
D
\alpha
R
7nAChR
alpha7nAChR
D
\alpha
R
7nAChR
alpha7nAChR
D
\alpha
R
7nAChR
alpha7nAChR
D
\alpha
R
7nAChR
alpha7nAChR
D
\alpha
R
7nAChR
alpha7nAChR
D
against the Simons Simplex Collection for autism spectrum disorder and
A
for neurodevelopment