Investigating the Role of Type I Interferons on the Central Nervous System in Aging

Cytokines are small protein signaling molecules secreted by immune cells in response to pathogens in order to increase communication and coordination between cells. Type I interferons (IFN-I), a class of antiviral and immunomodulatory cytokines, have been suggested to have another role as central nervous system (CNS) modulators as they have been shown to affect activity and excitability of neurons in vitro. A recent study provides evidence of elevated IFN-I production at the choroid plexus connected to age-associated cognitive decline (Baruch et al., 2014). However, little is currently known about the impact of age-associated increases in IFN-I production on specific cell types in the CNS and the functional effects on those cells. Here we show IFN-I production is elevated throughout the CNS and brain meninges using real-time qPCR. Flow cytometry confirmed the expression of the receptor for IFN-I, IFNAR1, on neurons at the protein level and immunohistochemistry indicated that downstream IFN-I signaling molecule IRF7 is present predominantly in astrocytes and to a lesser extent in neurons and microglia for both young and aged mice hippocampi. Neurons from aged mice showed significantly higher IRF7 expression than young mice. Functionally, young IFNAR-/- mice showed no significant differences in behavior in fear conditioning and open field, and only slight impairment in novel location recognition. fMRI showed no significant differences in hippocampal activity. Thus, our findings provide more evidence for aging-induced IFN-I signaling, expand the study of affected cell types in the hippocampus, and work to understand the role of IFN-I signaling in cognitive decline.