Graduation Year


Document Type




Degree Granting Department

Medical Sciences

Major Professor

Marcia Gordon

Co-Major Professor

Carmelina Gemma


Alzheimer's disease, CX3CR1, Fractalkine, Inflammation, Microglia, Parkinson's disease


As a consequence of aging, the brain is subject to chronic neuroinflammatory conditions. The resident immune cells of the brain, microglia, act similarly to peripheral macrophages to protect the brain from insults, infection, and physical trauma. However, without proper regulation of their respective host defense mechanisms, these actions can become neurotoxic. In the healthy brain neurons have several signaling systems that directly interact with microglia in order to maintain a calming influence upon their actions, one of particular interest is the chemokine CX3CL1. This chemokine is found predominantly on neurons, while its cognate receptor CX3CR1 is found exclusively on microglia. There has been a recent surge in literature as to the exact role CX3CL1 signaling plays various physiological and neuropathological animal models, with still no well-defined role. In an attempt to address the current discordance regarding the role of CX3CL1 signaling we have used three different models. The first examines how genetic ablation of CX3CR1 impacts hippocampal dependent cognitive function. Secondly, we examined the impact of chronic LPS-induced neuroinflammation affects CX3CL1 signaling and ultimately cognitive function. Lastly, we used an acute mouse model of Parkinson's disease induced by MPTP to examine the effects of specific subtypes of CX3CL1. Although three unique approaches were used to examine the anti-inflammatory properties of CX3CL1, parallels can be drawn from the separate studies as similar results were obtained. CX3CL1 signaling has significant anti-inflammatory actions within the brain and alterations that prevent this signaling to occur can result in impairments in cognitive function as well as exacerbation of neurodegenerative conditions.