Meeting Abstract

S9.10  Tuesday, Jan. 6  Neuroinflammation and behavioral deficits in the aged: Is microglial hyperactivity to blame? GODBOUT, JP; The Ohio State University, Columbus godbout.2@osu.edu

The bi-directional communication between the immune system and the CNS is necessary for mounting the appropriate immunological and behavioral responses to immune stimulation. Microglia, CNS innate immune cells, play an integral role in propagating inflammatory signals that are initiated at the periphery. Activation of peripheral innate immune cells elicits the secretion of inflammatory cytokines that use several distinct pathways to relay this signal to the CNS. This communication, in turn, induces microglia to produce the same cytokines, which target neuronal substrates and elicit a sickness behavior syndrome that is normally adaptive. In the elderly, however, systemic infection is associated with an increased frequency of behavioral and cognitive complications. We hypothesize that excessive cytokine production by microglia underlie these deficits. In support of this premise, we demonstrate that stimulation of the peripheral immune system in aged BALB/c mice causes exaggerated neuroinflammation that is paralleled by prolonged sickness and depressive-like behaviors. Moreover, our findings indicate that microglia become primed during normal aging with increased surface expression of MHC class II. Furthermore, minocycline, a purported microglia inhibitor, attenuates lipopolysaccharide (LPS)-induced exaggerated neuroinflammation and prolonged behavioral deficits in aged mice. Finally, peripheral LPS injection in aged mice causes exaggerated interleukin (IL)-1beta induction in primed (MHC II+) microglia. Taken together, these findings provide novel evidence that age-associated priming of microglia could play a pathophysiological role in the increased prevalence of neurobehavioral complications observed in the elderly.