Over an animals’s lifespan, microglia become more reactive or “primed”, worsening outcomes when an immune challenge is encountered (e.g. infection, surgery, or injury).

In modern society, sterile conditions may actually worsen inflammation. The immune system co-evolved with microorganisms, and underexposure to these organisms can harm immune function. Controlled reintroduction of microorganisms could improve the composition of the microbiome and lessen hyperactive inflammatory responses.

The Fonken lab is investigating mechanisms by which a vaccination of the soil bacterium, Mycobacterium vaccae, prevents exacerbated neuroinflammatory and behavioral deficits in aging.

This work is supported by NIH R01 AG062716

The circadian clock is a critical regulator of biological processes, generating cycles of hormone release, sleep-wake behaviors, and timing of cell division and repair. Microglia also express circadian timekeeping mechanisms, leading to daily cycles of high and low immune reactivity. With aging and Alzheimer’s Disease (AD), these rhythms dampen, possibility contributing to heightened neuroinflammation and pathology.

The Fonken lab is investigating how circadian rhythms in immune cell trafficking may become disrupted with age and AD-like pathology.

This work is supported by start NIH R01 AG078758

Alcohol use in aging populations is increasing. Excessive alcohol intake in aged individuals likely dysregulates immune dynamics in brain. The neuroimmune system critically regulates cognitive and behavioral changes with aging – pathological inflammatory reactivity occurs with neurodegenerative disorders and elicits cognitive decline. Along with Dr. Kimberly Nixon’s lab, we are investigating the mechanisms through which heavy, alcohol exposure increases vulnerability to age-associated neuropathology with a specific focus on phagocytic impairments in microglia.

This work is supported by R01AA032191.