Poster abstracts

Poster number 9 submitted by Christopher J. Henry

Minocycline attenuates LPS-induced exaggerated neuroinflammation and prolonged depressive-like behavior in aged mice

Christopher J. Henry (Molecular Virology, Immunology, and Medical Genetics; The Ohio State University), Yan Huang (Molecular Virology, Immunology, and Medical Genetics; The Ohio State University), Angela M. Wynne (Molecular Virology, Immunology, and Medical Genetics; The Ohio State University), Jonathan P. Godbout (Molecular Virology, Immunology, and Medical Genetics; The Ohio State University)

Abstract:
In the elderly, systemic infection is associated with an increased frequency of behavioral and cognitive complications. We have reported that peripheral innate immune activation with lipopolysaccharide (LPS) causes exaggerated neuroinflammation and prolonged sickness/depressive-like behaviors in aged BALB/c mice. The purpose of this study is to determine the role of microglia specifically in exaggerated neuroinflammation and to determine the extent to which minocycline (MN) attenuates LPS-induced microglia activation, sickness and depressive-like behavior in aged mice following innate immune activation. In the first study, adult (3-6 mo) aged (18-20 mo) BALB/c mice received an ip injection of E. coli LPS (0.33 mg/kg) and microglia were isolated from whole brain 4 h later. Microglial expression of IL-1beta and MHCII were determined. In the second study, aged (18-20 mo) BALB/c mice were pretreated with MN for three consecutive days and on the third day were also injected ip with saline or LPS. Sickness and depressive-like behavior were determined 72 h later. Microglia from aged brain expressed higher basal levels of MHCII and higher LPS-induced IL-1beta 4 h after LPS injection. Furthermore, MHCII⁺ microglia from aged mice exhibited robust IL-1beta expression following LPS injection. In addition, MN facilitated the recovery from sickness behavior (i.e. anorexia and weight loss) and attenuated LPS-induced depressive-like behavior in aged mice 72 h after LPS.

Keywords: mouse, aging, behavior