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Neuron-glia regulation of plasticity in health and neuroinflammatory diseases

Year:
2022
Duration:
36 months
Approved budget:
$1,197,310.48
Researchers:
Professor Wickliffe Abraham
,
Dr Shruthi Sateesh
,
Professor Anne La Flamme
Health issue:
Neurological (CNS)
Proposal type:
Project
Lay summary
Plasticity at synaptic junctions between nerve cells is fundamental to learning and memory. Such plasticity is generated not only by nerve cell activity, but it is also highly regulated by activity in nearby non-neural cells. In neurodegenerative diseases such as Alzheimer’s disease, the non-neural cells become pathologically reactive and drive brain inflammation. This unfortunately not only impairs synaptic plasticity and cognition, but it also amplifies the disease neurotoxicity when prolonged over time. Here we will study how non-neural cells work together with nerve cells to regulate synaptic plasticity normally in a brain region important for memory. Moreover, we will explore whether these mechanisms are aberrantly engaged in mouse models of frontotemporal dementia and multiple sclerosis, and whether a drug that reduces inflammation can rescue plasticity and memory to normal levels in these models.