Molecular and functional properties of cortical astrocytes during peripherally induced neuroinflammation

Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assessmedial 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.

Automated summary

The study explores the role of astrocytes in neuroinflammation triggered by peripheral bacterial endotoxin. Behavioral changes and astrocyte gene expression alterations peak with anhedonia and then return to normal levels. Despite significant astrocyte reactivity and behavioral changes, no evidence of altered neuronal survival or function in the PFC is found.