Summary
Multiple sclerosis (MS) is a devastating neurological condition affecting millions worldwide. Cognitive impairment significantly impacts the quality of life of people with MS and is often irreversible. Recent research suggests that overactive microglia, fuelled by altered metabolism, contribute to chronic inflammation and disrupt neuronal function. This PhD project will investigate the role of microglia in cognitive decline associated with MS.
Project aims
- Identify Metabolic Regulators of Microglial States: We will use a mouse model of MS to pinpoint metabolic factors that influence microglial activation in brain regions critical for cognition. Advanced imaging techniques will help us understand how microglia and neuronal networks change during chronic inflammation.
- Understand the Effects of Microglial Metabolism on Neurons: Using human cellular models, we will examine how manipulating microglial metabolism affects the function of human neurons. This will establish a direct link between microglial activity and neuronal health.
- Target Microglial Metabolism to Halt Cognitive Decline: Building on our findings, we will identify specific metabolic targets to modulate microglial activation. The goal is to redirect microglia from a harmful, inflammatory state to a protective one that supports neuronal function.
This research is a crucial step towards developing new therapies for cognitive decline in MS. By understanding the intricate relationship between microglial metabolism and neuronal health, we can potentially develop drugs and interventions that reduce inflammation and protect the brain's delicate balance. Additionally, our findings may have broader implications for other neurodegenerative diseases like Alzheimer's and Parkinson's, which also involve chronic central nervous system (CNS) inflammation and cognitive impairment.
Contact details
Dr Luca Peruzzotti Jametti (lp429@cam.ac.uk) – Neurology