86. The relation between body weight, brain inflammation, cognitive and emotional changes in response to an immune challenge

Abstract

Obesity is clearly a risk factor for increased basal inflammation and increased inflammatory responses to immune challenge. However, even weight variation within the normal range or in food-restricted animals is correlated with the immune response to a pathogen challenge and changes in behavior. We discovered that mice’s adverse responses to mold exposure were strongly correlated with body weight. In fact, small variations in body weight were better predictors of inflammation and/or cognitive effects than spore dose. Male C57Bl/6 mice were randomly assigned to treatment groups according to a stratified block design controlling for initial weight. Mice were nasally instilled with (1) intact Stachybotrys spores, (2) extracted spores that had their toxins removed and proteins denatured, or (3) saline vehicle three times per week. Their behavior was tested after three weeks of treatment, and the animals sacrificed and hippocampal tissue analyzed after six weeks. Weight did not differ across groups at any point in the experiment. However, the more the animals weighed, the higher the numbers of amoeboid microglia in the hippocampus, the greater the memory deficits on a contextual fear task, the higher the anxiety as measured on the elevated plus maze and the more fearful the animals were of the auditory cue that had been paired with one mild footshock. Clearly, weight within the normal range is a crucial variable in inflammatory responses leading to cognitive changes.