Fig. 11

The schematic above depicts a model in which beta-adrenergic receptors (adrb, β-ADR) modulate an A1 inflammatory response in astrocytes, which is upregulated in neurodegenerative disorders and with loss of noradrenergic tone. 5XFAD mice have increased levels of A1 inflammatory markers in the brain (Figs. 4A, 5A, 9A and 10A). Chemogenetic inhibition of the LC with inhibitory DREADD receptors (Fig. 4B) and antagonism of β2-ADRs (Fig. 5B) enhance the production of key A1-astrocytic chemokines and cytokines. Notably, conditional deletion of β2-ADR from microglia does not mimic the effect of β2-ADR antagonism or LC inhibition (Figs. 7B and 9B), indicating that NE might operate through ADRs on other cell types (e.g. astrocytes) to control neuroinflammation