Indiana University-Purdue University Indianapolis (IUPUI) / Chronic consumption of a high-fat diet is a lifestyle factor that increases the risk for cognitive impairment (Granholm et al., 2008; Greenwood & Winocur, 2005; Mattson, 2004; Winocur & Greenwood, 2005). A high-fat diet appears to facilitate cognitive impairment through the promotion of insulin resistance (Greenwood & Winocur, 2005; Stranahan et al., 2008; Winocur & Greenwood, 2005). A gap in the literature is an established timeframe of the progression and underlying mechanism, which study in animals would better afford. Furthermore, A limited number of studies have investigated the relationship between a high-fat diet and behavioral dysregulation such as anxiety and depression. The 1st aim of the study was to determine if consumption of a high-fat diet leads to cognitive impairment and behavioral dysfunction at 3, 8, or 13 weeks of consumption. The 2nd aim was to determine if cholesterol levels and HBP activity are aberrantly increased in specific regions in mice that display feeding induced cognitive/behavioral dysfunction. Consumption of the experimental specialty diets produced a number of significant behavioral effects. These significant effects began to emerge after only 3 weeks of low-and high-fat feeding with increased anxiety-like behavior displayed higher in the high-fat diet group for the Elevated Plus Maze and Open Field Test. There was increased thigmotactic behavior and floating in the low-fat diet group in the Morris Water Maze (MWM) task, therefore making cognitive assessment uninterpretable. This pattern in the behavioral tasks were more robust in the 8 week group and alleviated in the 13 week group. There was only a significant difference in depression-like symptoms in the Forced Swim (FS) Task in the 3 week group. Cholesterol analysis is still under review in Dr. Elmendorf’s lab to correlate cholesterol levels and cognitive/behavioral impairment.

The main objective of this study was to elucidate the possible mechanistic link between traumatic brain injury (TBI) and Alzheimer's disease (AD) using an animal model. We examined behavioral and histological effects of TBI in pre-symptomatic AD-transgenic mice (C57B6/SJL/SwissWebster/B6D2F1). In previous studies, these mice displayed AD-like behavioral deficits by 15-17 months of age and AD-like neuropathology as early as six months of age. To clarify the effects of TBI on these mice, the present study began when they were about three months of age and the study ended when they were about five months of age. As a control, non-transgenic (NT) mice were also evaluated in this study. To assess behavioral changes following TBI, all mice were subjected to 14 days of pre-TBI training of a spatial memory task, the radial arm water maze (RAWM). After training, there were no performance differences between AD-transgenic mice and NT mice. Then, half of the AD-transgenic mice, as well as half of the NT mice, received an experimental TBI at the right parietal cortex using a pneumatic impactor. The other half of these mice received sham surgery. At two, four, and six weeks after surgery, all mice were tested in the same water maze task and the numbers of errors were recorded. AD-transgenic mice with TBI made significantly more errors than AD-transgenic mice without TBI and NT mice regardless of TBI. Furthermore, deficits were observed at both two and six weeks after TBI surgery. To assess histological changes following TBI, we used a monoclonal antibody against beta-amyloid to detect AD-like plaques and an antibody against NeuN to evaluate the total neuronal loss. There were no clear group differences in terms of the beta amyloid expression pattern, although one AD-transgenic mouse with TBI showed AD-like beta amyloid plaques throughout the entire cortex and hippocampus. These results suggest that TBI precipitated behavioral deficits in a spatial memory task in pre-symptomatic AD-transgenic mice, but not control mice. Further studies are warranted for histological effects of TBI.