Activation of neuronal adenosine A1 receptors causes hypothermia through central and peripheral mechanisms

• DOI: 10.1371/journal.pone.0243986
• Publication Date: 2020-12-16T20:57:02Z
• Authors: Haley S. Province; Cuiying Xiao; Allison S. Mogul; Ankita Sahoo; Kenneth A. Jacobson; Ramón A. Piñol; Oksana Gavrilova; Marc L. Reitman
• Keywords: Adenosine A1 receptor

Extracellular adenosine, a danger signal, can cause hypothermia. We generated mice lacking neuronal adenosine A 1 receptors (A AR, encoded by the Adora1 gene) to examine contribution of these Intracerebroventricular injection selective AR agonist (Cl-ENBA, 5'-chloro-5'-deoxy- N 6 -endo-norbornyladenosine) produced hypothermia, which was reduced in with deletion neurons. non-brain penetrant [SPA, -(p-sulfophenyl) adenosine] also caused wild type but not suggesting that peripheral Mice expressing Cre recombinase from locus were investigate role specific cell populations body temperature regulation. Chemogenetic activation Adora1-Cre-expressing cells preoptic area did change temperature. In contrast, dorsomedial hypothalamus increased core temperature, concordant agonism at endogenous inhibitory causing These results suggest causes hypothermia via two distinct mechanisms: brain and on neurons outside blood-brain barrier. The variety mechanisms use induce underscores importance mouse response major metabolic stress or injury.