Abstract
Poly I:C, a viral mimetic, is a synthetic double-stranded RNA that is known to cause activation of the innate immune system, resulting in the emergence of sickness behaviors in otherwise healthy adult mice. However, the way in which such effects of poly I:C manifest themselves in aged mice are not currently known. We hypothesized that poly I:C administration would lead to burrowing deficits, but that these deficits would be exaggerated in aged subjects (19-months old) compared to young subjects (4-months old) that received the same dose. In order to associate these behavioral decrements with inflammatory factors, we measured mRNA expression of IL-1β and IL-6 in the hippocampus and parietal cortex and peripheral protein expression of IL-6, TNF-α, MCP-1, MIP-1α, and IL-1β in the serum. After exposure to poly I:C, aged subjects demonstrated significant impairments in their burrowing behavior, compared to younger subjects administered the same dose. These behavioral decrements coincided with increased expression of IL-6 among animals exposed to poly I:C and increased expression of IL-1β among aged animals in the hippocampus and cortex. Furthermore, we observed an increase in peripheral poly I:C-induced IL-6, TNF-α, MCP-1, and MIP-1α, but not IL-1β. These results indicate that virus-mediated immune activation in the aging body can lead to increased sickness behavior. Furthermore, these data indicated a possible dissociation between the effects of poly I:C on sickness behaviors in aged mice, with central expression of IL-1β potentially playing a role in age-related impairments.
► Compared sickness behavior utilizing burrowing in aged and young mice. ► Poly I:C administration leads to prolonged burrowing deficits in aged mice. ► Peripheral protein elevations in IL-6, TNF-α, MCP-1, and MIP-1α were observed. ► Elevated IL-1β and IL-6 mRNA were observed in the hippocampus and parietal cortex. ► IL-1β mRNA expression centrally may be associated with age-related deficits.