Neuroimmune signalling within and across brain borders regulating synaptic fate in neurodegeneration

Microglia, brain’s major resident macrophages, are critical contributors of neuronal synapse function and health. One important function of microglia is to detect, and determine, which synapses to eliminate and which ones to spare throughout lifespan, and that this function of microglia goes awry in multiple models of age-related neurodegenerative diseases to mediate synapse loss and dysfunction. However, what the triggers are that regulate microglia-synapse interaction in the adult and diseased brains are unclear. Recent findings, including those from our lab, collectively suggest that the functional cell states of microglia, including the synapse phagocytosing ones, are influenced by local synaptic activity, neighbouring astrocytes, and perivascular macrophages in mouse models of Alzheimer’s disease. I will highlight these works from our lab and in particular, I will present unpublished data involving cell-cell crosstalk between microglia and immune cells across brain borders that modulate synaptic fate.

SPEAKER BIOGRAPHY

The Hong lab studies neuro-glia-immune interactions at the synapse. In particular, the lab is interested in how brain’s glial cells including microglia and astrocytes coordinate neuronal synaptic homeostasis, and how this immune-glial crosstalk breaks down in disease, including in Alzheimer’s and Parkinson’s diseases (Bartels et al., Science 2020, Rueda-Carrasco, Sokolova and Lee et al., EMBO J 2020). The lab also studies neuroimmune signalling on and across brain borders and how they modulate neuronal and synaptic fate (De Schepper et al., Nature Neuroscience 2023).

Dr. Soyon Hong received her PhD in Neuroscience in 2012 from Harvard University, after studying with Dr. Dennis Selkoe on amyloid-induced synaptic degeneration (Hong et al., Neuron 2014, Hong et al., Journal of Neuroscience 2011, Li, Hong et al., Neuron 2011). Her post-doctoral work with Dr. Beth Stevens at Boston Children’s Hospital and Harvard Medical School led to the identification of microglia as cellular mediators of synapse loss in Alzheimer models via classical complement cascade (Hong et al., Science 2016). For these works, Soyon received the Junior Faculty Award at international ADPD Kenes (2015), Harvard Lefler Fellowship (2015-2017) and Charles King Trust Fellowship (2016-2018). Soyon started her independent lab at University College London in October 2018 as a UK DRI fellow (2018-2028). She was awarded Chan Zuckerberg Initiative (CZI) Neurodegeneration Challenge Network Collaborators Grant (2020-2026), and in 2023 was named the Alzheimer’s Research UK David Hague Early Career Investigator of the Year.