Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation

• Published in: Cell reports (Cambridge) Vol. 36; no. 6; p. 109508
• Main Authors: Diaz-Castro, Blanca, Bernstein, Alexander M., Coppola, Giovanni, Sofroniew, Michael V., Khakh, Baljit S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2021; Elsevier
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - pathology; anhedonia; Anhedonia - physiology; Animals; astrocyte; astrocyte reactivity; Astrocytes - metabolism; brain endothelial cell; Cell Communication; Cerebral Cortex - pathology; Inflammation - genetics; Inflammation - pathology; Lipopolysaccharides; LPS; Mice; Mice, Inbred C57BL; microglia; neuroinflammation; neuron; Neurons - pathology; Phenotype; prefrontal cortex; Pyramidal Cells - pathology; RNA-seq; Transcription, Genetic; RNA-seq; neuroinflammation; cell communication; prefrontal cortex; anhedonia; astrocyte reactivity; neuron; astrocyte; microglia; LPS; brain endothelial cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109508

Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes in mice following peripherally induced neuroinflammation triggered by a systemic bacterial endotoxin, lipopolysaccharide, which produces sickness-related behaviors, including anhedonia. Neuroinflammation-mediated behavioral changes and astrocyte-specific gene expression alterations peak when anhedonia is greatest and then reverse to normal. Notably, region-specific molecular identities of PFC and VCX astrocytes are largely maintained during reactivity changes. Gene pathway analyses reveal alterations of diverse cell signaling pathways, including changes in cell-cell interactions of multiple cell types that may underlie the central effects of neuroinflammation. Certain astrocyte molecular signatures accompanying neuroinflammation are shared with changes reported in Alzheimer’s disease and mouse models. However, we find no evidence of altered neuronal survival or function in the PFC even when neuroinflammation-induced astrocyte reactivity and behavioral changes are significant. [Display omitted] •Neuroinflammation causes reversible changes in mouse behavior and gene expression•Astrocytic region-specific signatures are maintained during neuroinflammation•Microglia and brain endothelial cells are the main responders•Neurons are largely normal during neuroinflammation-induced astrocyte reactivity Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. Diaz-Castro et al. report medial prefrontal cortex (PFC) and visual cortex (VCX) astrocyte and whole-tissue gene expression changes, as well as PFC neuronal properties, in mice following peripherally induced neuroinflammation triggered by a systemic bacterial endotoxin, lipopolysaccharide.