Lab focus
The brain has a high metabolic demand and consumes 20% of the body’s total energy supply despite weighing only 2% of the total body mass. Mitochondria are the cellular organelle that generate energy necessary to carry out normal cellular processes. Aberrant mitochondrial function results in further complications, generates reactive oxygen species, impaired turnover of damaged mitochondria that consequently result in cell and tissue damage. Mitochondrial metabolism and energy supply diminish as we age across tissues. In the brain, astrocytes are an important glial cell type that have an integral role in the maintenance and modulation of neuronal health and function by supplying important trophic factors and energy substrates necessary for normal function. The decline in energy utilization is associated with an increase in neuroinflammation and gliosis in the brain in both aging and in neurodegenerative diseases such as Alzheimer’s disease.
The Logan Lab is focused on understanding the cellular mechanisms underlying cognitive aging and neurodegeneration with a particular focus on the mitochondrial and metabolic disturbances that increase gliosis and neuroinflammation in the brain. Importantly cognitive function is not uniform and there is a great deal of heterogeneity in cognition in humans and animal models. Our studies have shown alterations in mitochondrial function and reactive gliosis with cognitive status (impaired vs. intact) in rodent models. To further understand the mechanisms that drive cognitive heterogeneity with age, we use cutting edge automated home-cage cognitive testing methodology to separate aged mice by cognitive status. We use innovative high-resolution respirometry to study mitochondrial function in isolated brain tissue coupled with single cell RNA sequencing and other molecular biology techniques. Using these advanced methodologies coupled with primary neuronal and astrocyte cell culture models, our lab aims to provide a wholistic understanding of the fundamental metabolic alterations in the brain from behavior to cell-specific alterations with age and neurodegenerative disorders.
Why it matters
Aging is the primary risk factor for Alzheimer's disease and other neurodegenerative disorders. In the United States, approximately two out of three Americans will experience some level of age-related cognitive impairment by age 70. Without successful interventions, individuals with cognitive impairment often rely on caretakers, leading to a profound socioeconomic impact. Importantly, not everyone experiences cognitive decline with age, suggesting there are protective factors that may provide resilience to a subset of individuals. This heterogeneity in cognitive function exists in mouse models, that can be leveraged to understand factors that mitigate healthy cognition versus those that drive impairment. Energy metabolism is at the heart of tissue function which when dysregulated can have severe detrimental effects. By understanding how metabolic alterations contribute to cognitive health our lab aims to delineate potential interventions to facilitate precision medicine.