Meningeal Lymphatic Vessels Contribute to Microglia Activation and Behavioral Response to Peripheral Inflammation

The recently discovered meningeal lymphatic system represents a potential point of access to the brain from the immune system that remains unexplored in the context of sickness behavior. Publications from our lab have established that meningeal lymphatic vessels facilitate solute clearance from the brain parenchyma and that these vessels deteriorate with age resulting in accumulation of protein aggregates as well as cognitive impairment. Additionally, age is a significant factor governing the severity of sickness behavior and late-life mood disorder diagnoses are strongly correlated with worse outcomes. These findings have spurred speculation that meningeal lymphatic function, sickness behavior, and psychiatric illness may be linked together therefore, a thorough understanding of meningeal lymphatic function and sickness behavior is essential to developing new strategies to treat cognitive decline and mood disorders. To summarize, the basis of this thesis is to address the following three experimental
questions:
1. What are the cellular targets and sources of IL-1β in the CNS involved in the
behavioral response to peripheral inflammation?
2. Do meningeal lymphatic vessels contribute to the behavioral response to
peripheral inflammation?
3. Does meningeal lymphatic impairment contribute to the exaggerated response to
peripheral inflammation observed in aged mice?