Diet-induced obesity prolongs neuroinflammation and recruits CCR2(+) monocytes to the brain following herpes simplex virus (HSV)-1 latency in mice.
Herpes simplex virus (HSV)-1 is a ubiquitous human infection, with increased prevalence in obese populations. Obesity has been linked to increased inflammation, susceptibility to infection, and higher rates of anxiety disorder and cognitive impairment. To determine how obesity alters neuroinflammation and behavior following infection, we infected weanling C57BL/6 or CCR2(RFP/+)/CX3CR1(GFP/+) mice with a very low dose of HSV-1. Following viral latency (14days post infection (d p.i.)), mice were randomly assigned to remain on the low fat (LF) diet or switched to a 45% high fat (HF) diet. Eight weeks post diet shift, latently infected mice on the HF diet (HSV-HF) had greater microglial activation and infiltration of inflammatory CCR2(+) monocytes in the hypothalamus and dentate gyrus, in comparison to both HSV-LF mice and uninfected mice on LF and HF diets. VCAM staining was present in hypothalamus and hippocampus of the HSV-HF mice in the areas of monocyte infiltration. Infiltrating monocytes also produced proinflammatory cytokines demonstrating that, along with activated microglia, monocytes contribute to sustained neuroinflammation in latently infected obese mice. Utilizing a light-dark preference test, we found that HSV-HF mice had increased anxiety-like behavior. In the marble-burying test, HF diet and HSV infection resulted in increased numbers of buried marbles. Together, these mice provide a useful, testable model to study the biobehavioral effects of obesity and latent HSV-1 infection in regards to anxiety and may provide a tool for studying diet intervention programs in the future.
Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States.
Katherine A
KA
White
University of North Carolina Neuroscience Center, Chapel Hill, NC, United States.
Scott R
SR
Hutton
Children's Health Research Center, Sanford Research, Sioux Falls, SD, United States.
Jill M
JM
Weimer
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, NC, United States. Electronic address: patti@email.unc.edu.
Patricia A
PA
Sheridan
D000818:Animals; D001007:Anxiety / Q000276:immunology*; D001522:Behavior, Animal / Q000502:physiology*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009765:Obesity / Q000276:immunology*; D054390:Receptors, CCR2
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2
Anxiety; HSV-1; Microglia and macrophage; Neuroinflammation; Obesity