Dr. Patricia Sheridan Combines Neuroscience and Nutrition
Watch Dr. Sheridan discuss her research.
Dr. Sheridan’s research can be broadly described as determining how diet alters inflammatory processes in the brain. Dr. Sheridan’s project “Vitamin E, T Cell Trafficking and the Development of HSV-1 Encephalitis” is designed to investigate the mechanism(s) by which vitamin E (VE) influences T cell trafficking and the subsequent pathological outcome following herpes simplex virus (HSV)-1 infection. A second focus of Dr. Sheridan’s research is the role diet plays in altering the activation of microglia (the brain’s macrophage). Microglia make up approximately 10-15% of the cells of the brain. These bone-marrow derived immune cells play a critical role in regulating the immune system to brain communication under both homeostatic and pathological conditions. In response to an insult, microglia produce several inflammatory mediators including pro-inflammatory cytokines, reactive oxygen species, eicosanoids and excitatory amino acids. The “controlled” production of these mediators resolves and repairs the damage done by the insult to the neurons of the CNS. In contrast, an “uncontrolled” or continued activation of this response results in excessive neuronal damage and neurodegeneration. Currently, Dr. Sheridan’s studies that focus on microglia are: 1) determining how VE deficiency results in increased activation of microglia during HSV-1 infection and the role of oxidative stress in this process 2) determining whether the consumption of a high fat diet results in microglial activation leading to increased neuroinflammation and neurodegeneration in the brain. Focusing on the role of high fat diet (HF) consumption on neuroinflammation, we are finding that microglia isolated from the brains of mice on the HF diet have increased expression of markers of inflammation. These markers include toll-like receptor (TLR)2 and TLR4. The increase in TLR4/MD2 is an important finding as the complexing of these proteins is critical for inflammatory signaling in microglia due to the binding of Alzheimer’s disease protein, Aβ. These data suggest that the brains of the mice on the high fat diet will be more susceptible to neuronal damage during an infection or pathological processes that lead to neurodegenerative disease. These studies will answer questions important to understanding how diet and obesity affect brain function. As our population ages and becomes increasingly obese, the implications of diet on age-related neurological conditions are a significant public health concern.