The Barrientos laboratory focuses on the vulnerabilities of the normal aging brain that, when challenged, lead to long-lasting memory deficits. The lab has examined various triggers such as bacterial infection, surgery, and high-fat diet that induce exaggerated and prolonged neuroinflammation in discrete regions of the aged brain. We have identified sensitized microglia as playing a key role in this exaggerated response. This potentiated neuroinflammatory response causes robust inhibition of brain-derived neurotrophic factor (BDNF) and long-term potentiation (LTP) in the hippocampus, two mechanisms critical to forming long-term memories. Furthermore, we have demonstrated that behavioral interventions such as exercise and reducing saturated fats from the diet can desensitize microglia, normalize the inflammatory response in the brain, and protect memory function.
The primary focus of the lab uses a rat model of postoperative cognitive dysfunction (POCD) to examine the mechanisms that may underlie persistent cognitive declines that occur in aged patients following a surgical procedure, and lead to Alzheimer’s disease. The roles that opiates, microglia, and toll-like receptor 4 play in this long-lasting neuroinflammatory condition are being examined.
The second major project of the lab is to investigate high-fat (and other unhealthy) diet-induced memory declines in aging. To date, we have discovered that a short time (3 days) on a high-fat diet produces a robust neuroinflammatory response in the aged brain, causing a wide-range of cognitive deficits. Moving forward, we will be examining the pathways and mechanisms that drive and/or contribute to these effects.
The third major project of the lab is a collaborative project with Dr. Leah Pyter’s laboratory to determine the neuroinflammatory sequelae and associated behavioral declines in aged female mice in a model of breast cancer. We are characterizing various behaviors including learning and memory, locomotion, and anxiety. Also, we are using various molecular biological techniques to measure gene and protein expression of many inflammatory and aging related molecules in key regions of the brain.