Poster abstracts

Poster number 105 submitted by Christopher Henry

Minocycline suppression of microglial activation attenuates lipopolysaccharide-induced neuroinflammation, sickness behavior, and anhedonia

Christopher J. Henry (MVIMG, The Ohio State University), Yan Huang, Angela M. Wynne (MVIMG, The Ohio State University), Mark Hanke (Oral Biology, The Ohio State University), Michael T. Bailey, John F. Sheridan (IBMR, Oral Biology, The Ohio State University), Jonathan P. Godbout (IBMR, MVIMG, The Ohio State University)

Abstract:
Activation of the peripheral innate immune system stimulates the production of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive or prolonged production of CNS cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, a purported microglial inhibitor, attenuates LPS-induced neuroinflammation, sickness behavior, and anhedonia. In the first set of experiments the effect of minocycline pretreatment on LPS-induced microglia activation was assessed in BV-2 microglia cell cultures. We confirmed that minocycline attenuated LPS-stimulated inflammatory cytokine expression and secretion in BV-2 cells. In the second set of experiments, BALB/c mice were pretreated with minocycline prior to peripheral LPS injection. Our data show that minocycline reduced LPS-induced Toll-like receptor 2 (TLR2) surface expression on brain microglia. Moreover, minocycline facilitated the recovery from sickness behavior (i.e., anorexia, weight loss, and social withdrawal) and prevented anhedonia in adult mice challenged with LPS. Furthermore, the minocycline-associated recovery from LPS-induced sickness behavior was paralleled by reduced mRNA levels of Interleukin (IL)-1beta, IL-6, and indoleamine 2,3 dioxygenase (IDO) in the cortex and hippocampus. Finally, in aged mice, where exaggerated neuroinflammation was elicited by LPS, minocycline pretreatment was still effective in markedly reducing mRNA levels of IL-1beta, TLR2, and IDO in the hippocampus. These data indicate that minocycline mitigates neuroinflammation in the adult and aged brain and modulates the cytokine-associated changes in motivation and behavior.

Keywords: minocycline, neuroinflammation, microglia